Abstract

Nanoparticle (NP) based technologies have proved to be considerably beneficial for advances in biomedicine especially in the areas of disease detection, drug delivery and bioimaging. Over the last few decades, NPs have garnered interest for their exemplary impacts on the detection, treatment, and prevention of cancer. The full potential of these technologies are yet to be employed for clinical use. The ongoing research and development in this field demands single multifunctional composite materials that can be employed simultaneously for drug delivery and biomedical imaging. In this manuscript, a unique combination of silk fibroin (SF) and nanodiamonds (NDs) in the form of nanospheres are fabricated and investigated. The spheres were loaded with the anthracyline Doxorubicin (DoX) and the drug release kinetics for these ND-SF-DoX (NDSX) spheres were studied. NDs provided the fluorescence modality for imaging while the degradable SF spheres stabilized and released the drug in a controlled manner. The emission and structural properties of the spheres were characterized during drug release. The degradability of SF and the subsequent release of DoX from the spheres were monitored through fluorescence of NDs inside the spheres. This research demonstrates the enormous potential of the ND-SF nanocomposite platforms for diagnostic and therapeutic purposes, which are both important for pharmaceutical research and clinical settings.

© 2015 Optical Society of America

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References

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2015 (4)

V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
[Crossref] [PubMed]

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

J. Brown, C.-L. Lu, J. Coburn, and D. L. Kaplan, “Impact of silk biomaterial structure on proteolysis,” Acta Biomater. 11, 212–221 (2015).
[Crossref] [PubMed]

A. Khalid, K. Chung, R. Rajasekharan, D. W. M. Lau, T. J. Karle, B. C. Gibson, and S. Tomljenovic-Hanic, “Lifetime Reduction and Enhanced Emission of Single Photon Color Centers in Nanodiamond via Surrounding Refractive Index Modification,” Sci. Rep. 5, 11179 (2015).
[Crossref] [PubMed]

2014 (7)

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

A. Khalid, R. Lodin, P. Domachuk, H. Tao, J. E. Moreau, D. L. Kaplan, F. G. Omenetto, B. C. Gibson, and S. Tomljenovic-Hanic, “Synthesis and characterization of biocompatible nanodiamond-silk hybrid material,” Biomed. Opt. Express 5(2), 596–608 (2014).
[Crossref] [PubMed]

Y. Y. Hui, L.-J. Su, O. Y. Chen, Y.-T. Chen, T.-M. Liu, and H.-C. Chang, “Wide-field imaging and flow cytometric analysis of cancer cells in blood by fluorescent nanodiamond labeling and time gating,” Sci. Rep. 4, 5574 (2014).
[Crossref] [PubMed]

A. Florczak, A. Mackiewicz, and H. Dams-Kozlowska, “Functionalized spider silk spheres as drug carriers for targeted cancer therapy,” Biomacromolecules 15(8), 2971–2981 (2014).
[Crossref] [PubMed]

X. Zeng, R. Morgenstern, and A. M. Nyström, “Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-mediated drug resistance,” Biomaterials 35(4), 1227–1239 (2014).
[Crossref] [PubMed]

C. Harrison, “Anticancer drugs: double boost for doxorubicin therapy,” Nat. Rev. Drug Discov. 13, 178 (2014).
[PubMed]

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

2013 (6)

F. P. Seib, E. M. Pritchard, and D. L. Kaplan, “Self-assembling doxorubicin silk hydrogels for the focal treatment of primary breast cancer,” Adv. Funct. Mater. 23(1), 58–65 (2013).
[Crossref] [PubMed]

F. P. Seib and D. L. Kaplan, “Silk for drug delivery applications: opportunities and challenges,” Isr. J. Chem. 53, 756–766 (2013).

F. P. Seib, G. T. Jones, J. Rnjak-Kovacina, Y. Lin, and D. L. Kaplan, “pH-dependent anticancer drug release from silk nanoparticles,” Adv. Healthc. Mater. 2(12), 1606–1611 (2013).
[Crossref] [PubMed]

H. Maeda, “The link between infection and cancer: tumor vasculature, free radicals, and drug delivery to tumors via the EPR effect,” Cancer Sci. 104(7), 779–789 (2013).
[Crossref] [PubMed]

J. Liu, M. Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng, “Passive Tumor Targeting of Renal-Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance,” J. Am. Chem. Soc. 135(13), 4978–4981 (2013).
[Crossref] [PubMed]

M. A. Zurbuchen, M. P. Lake, S. A. Kohan, B. Leung, and L.-S. Bouchard, “Nanodiamond Landmarks for Subcellular Multimodal Optical and Electron Imaging,” Sci. Rep. 3, 2668 (2013).
[Crossref] [PubMed]

2012 (3)

H. Tao, D. L. Kaplan, and F. G. Omenetto, “Silk Materials - A Road to Sustainable High Technology,” Adv. Mater. 24(21), 2824–2837 (2012).
[Crossref] [PubMed]

I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
[Crossref]

F. P. Seib and D. L. Kaplan, “Doxorubicin-loaded silk films: Drug-silk interactions and in vivo performance in human orthotopic breast cancer,” Biomaterials 33(33), 8442–8450 (2012).
[Crossref] [PubMed]

2011 (4)

H.-Y. Youn, D. J. McCanna, J. G. Sivak, and L. W. Jones, “In vitro ultraviolet-induced damage in human corneal, lens, and retinal pigment epithelial cells,” Mol. Vis. 17, 237–246 (2011).
[PubMed]

E. Wenk, H. P. Merkle, and L. Meinel, “Silk fibroin as a vehicle for drug delivery applications,” J. Control. Release 150(2), 128–141 (2011).
[Crossref] [PubMed]

E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
[Crossref] [PubMed]

D. N. Rockwood, R. C. Preda, T. Yücel, X. Wang, M. L. Lovett, and D. L. Kaplan, “Materials fabrication from Bombyx mori silk fibroin,” Nat. Protoc. 6(10), 1612–1631 (2011).
[Crossref] [PubMed]

2010 (3)

X. Wang, T. Yucel, Q. Lu, X. Hu, and D. L. Kaplan, “Silk nanospheres and microspheres from silk/pva blend films for drug delivery,” Biomaterials 31(6), 1025–1035 (2010).
[Crossref] [PubMed]

P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
[Crossref] [PubMed]

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

2009 (2)

A. S. Barnard, “Diamond standard in diagnostics: nanodiamond biolabels make their mark,” Analyst (Lond.) 134(9), 1751–1764 (2009).
[Crossref] [PubMed]

X. Fei and Y. Gu, “Progress in modifications and applications of fluorescent dye probe,” Prog. Nat. Sci. 19(1), 1–7 (2009).
[Crossref]

2008 (2)

S. Myung, H.-S. Kim, Y. Kim, P. Chen, and H.-J. Jin, “Fluorescent silk fibroin nanoparticles prepared using a reverse microemulsion,” Macromol. Res. 16(7), 604–608 (2008).
[Crossref]

F. G. Omenetto and D. L. Kaplan, “A new route for silk,” Nat. Photonics 2(11), 641–643 (2008).
[Crossref]

2007 (2)

X. Wang, E. Wenk, A. Matsumoto, L. Meinel, C. Li, and D. L. Kaplan, “Silk microspheres for encapsulation and controlled release,” J. Control. Release 117(3), 360–370 (2007).
[Crossref] [PubMed]

A. M. Rahman, S. W. Yusuf, and M. S. Ewer, “Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation,” Int. J. Nanomedicine 2(4), 567–583 (2007).
[PubMed]

2006 (1)

D. Missirlis, R. Kawamura, N. Tirelli, and J. A. Hubbell, “Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles,” Eur. J. Pharm. Sci. 29(2), 120–129 (2006).
[Crossref] [PubMed]

2005 (2)

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
[Crossref] [PubMed]

M. Ferrari, “Cancer nanotechnology: opportunities and challenges,” Nat. Rev. Cancer 5(3), 161–171 (2005).
[Crossref] [PubMed]

2003 (1)

G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
[Crossref] [PubMed]

2001 (1)

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

1996 (1)

T. Sakakibara, H. K. Fangn Chen, K. Kunieda, R. E. Cuenca, A. F. J. Martin, and R. B. Bankert, “Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts,” Cancer Res. 56, 3743 (1996).

1993 (1)

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

1979 (1)

R. T. Chlebowski, “Adriamycin (Doxorubicin) Cardiotoxicity: A Review,” West. J. Med. 131(5), 364–368 (1979).
[PubMed]

Algieri, F.

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

Altman, G. H.

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
[Crossref] [PubMed]

G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
[Crossref] [PubMed]

Antle, K.

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
[Crossref] [PubMed]

Baati, T.

P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
[Crossref] [PubMed]

Bankert, R. B.

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E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
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S. Myung, H.-S. Kim, Y. Kim, P. Chen, and H.-J. Jin, “Fluorescent silk fibroin nanoparticles prepared using a reverse microemulsion,” Macromol. Res. 16(7), 604–608 (2008).
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J. Brown, C.-L. Lu, J. Coburn, and D. L. Kaplan, “Impact of silk biomaterial structure on proteolysis,” Acta Biomater. 11, 212–221 (2015).
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I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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X. Fei and Y. Gu, “Progress in modifications and applications of fluorescent dye probe,” Prog. Nat. Sci. 19(1), 1–7 (2009).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
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A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
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A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
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A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
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E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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X. Fei and Y. Gu, “Progress in modifications and applications of fluorescent dye probe,” Prog. Nat. Sci. 19(1), 1–7 (2009).
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K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
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E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
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R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
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G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
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M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
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K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
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G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
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S. Myung, H.-S. Kim, Y. Kim, P. Chen, and H.-J. Jin, “Fluorescent silk fibroin nanoparticles prepared using a reverse microemulsion,” Macromol. Res. 16(7), 604–608 (2008).
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Kaplan, D. L.

J. Brown, C.-L. Lu, J. Coburn, and D. L. Kaplan, “Impact of silk biomaterial structure on proteolysis,” Acta Biomater. 11, 212–221 (2015).
[Crossref] [PubMed]

A. Khalid, R. Lodin, P. Domachuk, H. Tao, J. E. Moreau, D. L. Kaplan, F. G. Omenetto, B. C. Gibson, and S. Tomljenovic-Hanic, “Synthesis and characterization of biocompatible nanodiamond-silk hybrid material,” Biomed. Opt. Express 5(2), 596–608 (2014).
[Crossref] [PubMed]

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

F. P. Seib and D. L. Kaplan, “Silk for drug delivery applications: opportunities and challenges,” Isr. J. Chem. 53, 756–766 (2013).

F. P. Seib, G. T. Jones, J. Rnjak-Kovacina, Y. Lin, and D. L. Kaplan, “pH-dependent anticancer drug release from silk nanoparticles,” Adv. Healthc. Mater. 2(12), 1606–1611 (2013).
[Crossref] [PubMed]

F. P. Seib, E. M. Pritchard, and D. L. Kaplan, “Self-assembling doxorubicin silk hydrogels for the focal treatment of primary breast cancer,” Adv. Funct. Mater. 23(1), 58–65 (2013).
[Crossref] [PubMed]

F. P. Seib and D. L. Kaplan, “Doxorubicin-loaded silk films: Drug-silk interactions and in vivo performance in human orthotopic breast cancer,” Biomaterials 33(33), 8442–8450 (2012).
[Crossref] [PubMed]

H. Tao, D. L. Kaplan, and F. G. Omenetto, “Silk Materials - A Road to Sustainable High Technology,” Adv. Mater. 24(21), 2824–2837 (2012).
[Crossref] [PubMed]

D. N. Rockwood, R. C. Preda, T. Yücel, X. Wang, M. L. Lovett, and D. L. Kaplan, “Materials fabrication from Bombyx mori silk fibroin,” Nat. Protoc. 6(10), 1612–1631 (2011).
[Crossref] [PubMed]

X. Wang, T. Yucel, Q. Lu, X. Hu, and D. L. Kaplan, “Silk nanospheres and microspheres from silk/pva blend films for drug delivery,” Biomaterials 31(6), 1025–1035 (2010).
[Crossref] [PubMed]

F. G. Omenetto and D. L. Kaplan, “A new route for silk,” Nat. Photonics 2(11), 641–643 (2008).
[Crossref]

X. Wang, E. Wenk, A. Matsumoto, L. Meinel, C. Li, and D. L. Kaplan, “Silk microspheres for encapsulation and controlled release,” J. Control. Release 117(3), 360–370 (2007).
[Crossref] [PubMed]

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
[Crossref] [PubMed]

G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
[Crossref] [PubMed]

Karle, T. J.

A. Khalid, K. Chung, R. Rajasekharan, D. W. M. Lau, T. J. Karle, B. C. Gibson, and S. Tomljenovic-Hanic, “Lifetime Reduction and Enhanced Emission of Single Photon Color Centers in Nanodiamond via Surrounding Refractive Index Modification,” Sci. Rep. 5, 11179 (2015).
[Crossref] [PubMed]

Kawamura, R.

D. Missirlis, R. Kawamura, N. Tirelli, and J. A. Hubbell, “Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles,” Eur. J. Pharm. Sci. 29(2), 120–129 (2006).
[Crossref] [PubMed]

Kawashima, Y.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Khalid, A.

A. Khalid, K. Chung, R. Rajasekharan, D. W. M. Lau, T. J. Karle, B. C. Gibson, and S. Tomljenovic-Hanic, “Lifetime Reduction and Enhanced Emission of Single Photon Color Centers in Nanodiamond via Surrounding Refractive Index Modification,” Sci. Rep. 5, 11179 (2015).
[Crossref] [PubMed]

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

A. Khalid, R. Lodin, P. Domachuk, H. Tao, J. E. Moreau, D. L. Kaplan, F. G. Omenetto, B. C. Gibson, and S. Tomljenovic-Hanic, “Synthesis and characterization of biocompatible nanodiamond-silk hybrid material,” Biomed. Opt. Express 5(2), 596–608 (2014).
[Crossref] [PubMed]

Kim, H.-S.

S. Myung, H.-S. Kim, Y. Kim, P. Chen, and H.-J. Jin, “Fluorescent silk fibroin nanoparticles prepared using a reverse microemulsion,” Macromol. Res. 16(7), 604–608 (2008).
[Crossref]

Kim, S.

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

Kim, S. V.

V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
[Crossref] [PubMed]

Kim, Y.

S. Myung, H.-S. Kim, Y. Kim, P. Chen, and H.-J. Jin, “Fluorescent silk fibroin nanoparticles prepared using a reverse microemulsion,” Macromol. Res. 16(7), 604–608 (2008).
[Crossref]

Kimura, R.

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Kohan, S. A.

M. A. Zurbuchen, M. P. Lake, S. A. Kohan, B. Leung, and L.-S. Bouchard, “Nanodiamond Landmarks for Subcellular Multimodal Optical and Electron Imaging,” Sci. Rep. 3, 2668 (2013).
[Crossref] [PubMed]

Kreuz, C.

P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
[Crossref] [PubMed]

Kunieda, K.

T. Sakakibara, H. K. Fangn Chen, K. Kunieda, R. E. Cuenca, A. F. J. Martin, and R. B. Bankert, “Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts,” Cancer Res. 56, 3743 (1996).

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Lake, M. P.

M. A. Zurbuchen, M. P. Lake, S. A. Kohan, B. Leung, and L.-S. Bouchard, “Nanodiamond Landmarks for Subcellular Multimodal Optical and Electron Imaging,” Sci. Rep. 3, 2668 (2013).
[Crossref] [PubMed]

Lam, R.

E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
[Crossref] [PubMed]

Lammers, T.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Lamprecht, A.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Lau, D. W. M.

A. Khalid, K. Chung, R. Rajasekharan, D. W. M. Lau, T. J. Karle, B. C. Gibson, and S. Tomljenovic-Hanic, “Lifetime Reduction and Enhanced Emission of Single Photon Color Centers in Nanodiamond via Surrounding Refractive Index Modification,” Sci. Rep. 5, 11179 (2015).
[Crossref] [PubMed]

Lee, D. K.

V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
[Crossref] [PubMed]

Lehr, C. M.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Leung, B.

M. A. Zurbuchen, M. P. Lake, S. A. Kohan, B. Leung, and L.-S. Bouchard, “Nanodiamond Landmarks for Subcellular Multimodal Optical and Electron Imaging,” Sci. Rep. 3, 2668 (2013).
[Crossref] [PubMed]

Li, C.

X. Wang, E. Wenk, A. Matsumoto, L. Meinel, C. Li, and D. L. Kaplan, “Silk microspheres for encapsulation and controlled release,” J. Control. Release 117(3), 360–370 (2007).
[Crossref] [PubMed]

Lin, Y.

F. P. Seib, G. T. Jones, J. Rnjak-Kovacina, Y. Lin, and D. L. Kaplan, “pH-dependent anticancer drug release from silk nanoparticles,” Adv. Healthc. Mater. 2(12), 1606–1611 (2013).
[Crossref] [PubMed]

Liu, J.

J. Liu, M. Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng, “Passive Tumor Targeting of Renal-Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance,” J. Am. Chem. Soc. 135(13), 4978–4981 (2013).
[Crossref] [PubMed]

Liu, T.-M.

Y. Y. Hui, L.-J. Su, O. Y. Chen, Y.-T. Chen, T.-M. Liu, and H.-C. Chang, “Wide-field imaging and flow cytometric analysis of cancer cells in blood by fluorescent nanodiamond labeling and time gating,” Sci. Rep. 4, 5574 (2014).
[Crossref] [PubMed]

Lodin, R.

Lovett, M. L.

D. N. Rockwood, R. C. Preda, T. Yücel, X. Wang, M. L. Lovett, and D. L. Kaplan, “Materials fabrication from Bombyx mori silk fibroin,” Nat. Protoc. 6(10), 1612–1631 (2011).
[Crossref] [PubMed]

Lozano-Pérez, A. A.

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

Lu, C.-L.

J. Brown, C.-L. Lu, J. Coburn, and D. L. Kaplan, “Impact of silk biomaterial structure on proteolysis,” Acta Biomater. 11, 212–221 (2015).
[Crossref] [PubMed]

Lu, H.

G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
[Crossref] [PubMed]

Lu, Q.

X. Wang, T. Yucel, Q. Lu, X. Hu, and D. L. Kaplan, “Silk nanospheres and microspheres from silk/pva blend films for drug delivery,” Biomaterials 31(6), 1025–1035 (2010).
[Crossref] [PubMed]

Mackiewicz, A.

A. Florczak, A. Mackiewicz, and H. Dams-Kozlowska, “Functionalized spider silk spheres as drug carriers for targeted cancer therapy,” Biomacromolecules 15(8), 2971–2981 (2014).
[Crossref] [PubMed]

Maeda, H.

H. Maeda, “The link between infection and cancer: tumor vasculature, free radicals, and drug delivery to tumors via the EPR effect,” Cancer Sci. 104(7), 779–789 (2013).
[Crossref] [PubMed]

Maincent, P.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Marelli, B.

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

Marsaud, V.

P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
[Crossref] [PubMed]

Martin, A. F. J.

T. Sakakibara, H. K. Fangn Chen, K. Kunieda, R. E. Cuenca, A. F. J. Martin, and R. B. Bankert, “Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts,” Cancer Res. 56, 3743 (1996).

Matsumoto, A.

X. Wang, E. Wenk, A. Matsumoto, L. Meinel, C. Li, and D. L. Kaplan, “Silk microspheres for encapsulation and controlled release,” J. Control. Release 117(3), 360–370 (2007).
[Crossref] [PubMed]

McCanna, D. J.

H.-Y. Youn, D. J. McCanna, J. G. Sivak, and L. W. Jones, “In vitro ultraviolet-induced damage in human corneal, lens, and retinal pigment epithelial cells,” Mol. Vis. 17, 237–246 (2011).
[PubMed]

Meinel, L.

E. Wenk, H. P. Merkle, and L. Meinel, “Silk fibroin as a vehicle for drug delivery applications,” J. Control. Release 150(2), 128–141 (2011).
[Crossref] [PubMed]

X. Wang, E. Wenk, A. Matsumoto, L. Meinel, C. Li, and D. L. Kaplan, “Silk microspheres for encapsulation and controlled release,” J. Control. Release 117(3), 360–370 (2007).
[Crossref] [PubMed]

Merkle, H. P.

E. Wenk, H. P. Merkle, and L. Meinel, “Silk fibroin as a vehicle for drug delivery applications,” J. Control. Release 150(2), 128–141 (2011).
[Crossref] [PubMed]

Militao, G. C. G.

I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
[Crossref]

Missirlis, D.

D. Missirlis, R. Kawamura, N. Tirelli, and J. A. Hubbell, “Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles,” Eur. J. Pharm. Sci. 29(2), 120–129 (2006).
[Crossref] [PubMed]

Mitropoulos, A. N.

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

Moreau, J. E.

A. Khalid, R. Lodin, P. Domachuk, H. Tao, J. E. Moreau, D. L. Kaplan, F. G. Omenetto, B. C. Gibson, and S. Tomljenovic-Hanic, “Synthesis and characterization of biocompatible nanodiamond-silk hybrid material,” Biomed. Opt. Express 5(2), 596–608 (2014).
[Crossref] [PubMed]

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
[Crossref] [PubMed]

Morgenstern, R.

X. Zeng, R. Morgenstern, and A. M. Nyström, “Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-mediated drug resistance,” Biomaterials 35(4), 1227–1239 (2014).
[Crossref] [PubMed]

Myung, S.

S. Myung, H.-S. Kim, Y. Kim, P. Chen, and H.-J. Jin, “Fluorescent silk fibroin nanoparticles prepared using a reverse microemulsion,” Macromol. Res. 16(7), 604–608 (2008).
[Crossref]

Nakatani, S.

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Ning, X.

J. Liu, M. Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng, “Passive Tumor Targeting of Renal-Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance,” J. Am. Chem. Soc. 135(13), 4978–4981 (2013).
[Crossref] [PubMed]

Nyström, A. M.

X. Zeng, R. Morgenstern, and A. M. Nyström, “Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-mediated drug resistance,” Biomaterials 35(4), 1227–1239 (2014).
[Crossref] [PubMed]

Omenetto, F. G.

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

A. Khalid, R. Lodin, P. Domachuk, H. Tao, J. E. Moreau, D. L. Kaplan, F. G. Omenetto, B. C. Gibson, and S. Tomljenovic-Hanic, “Synthesis and characterization of biocompatible nanodiamond-silk hybrid material,” Biomed. Opt. Express 5(2), 596–608 (2014).
[Crossref] [PubMed]

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

H. Tao, D. L. Kaplan, and F. G. Omenetto, “Silk Materials - A Road to Sustainable High Technology,” Adv. Mater. 24(21), 2824–2837 (2012).
[Crossref] [PubMed]

F. G. Omenetto and D. L. Kaplan, “A new route for silk,” Nat. Photonics 2(11), 641–643 (2008).
[Crossref]

Ortiz-Cullera, V.

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

Osawa, E.

E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
[Crossref] [PubMed]

Perotto, G.

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

Preda, R. C.

D. N. Rockwood, R. C. Preda, T. Yücel, X. Wang, M. L. Lovett, and D. L. Kaplan, “Materials fabrication from Bombyx mori silk fibroin,” Nat. Protoc. 6(10), 1612–1631 (2011).
[Crossref] [PubMed]

Pritchard, E. M.

F. P. Seib, E. M. Pritchard, and D. L. Kaplan, “Self-assembling doxorubicin silk hydrogels for the focal treatment of primary breast cancer,” Adv. Funct. Mater. 23(1), 58–65 (2013).
[Crossref] [PubMed]

Rahman, A. M.

A. M. Rahman, S. W. Yusuf, and M. S. Ewer, “Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation,” Int. J. Nanomedicine 2(4), 567–583 (2007).
[PubMed]

Rajasekharan, R.

A. Khalid, K. Chung, R. Rajasekharan, D. W. M. Lau, T. J. Karle, B. C. Gibson, and S. Tomljenovic-Hanic, “Lifetime Reduction and Enhanced Emission of Single Photon Color Centers in Nanodiamond via Surrounding Refractive Index Modification,” Sci. Rep. 5, 11179 (2015).
[Crossref] [PubMed]

Richmond, J.

G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
[Crossref] [PubMed]

Rijcken, C. J.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Rnjak-Kovacina, J.

F. P. Seib, G. T. Jones, J. Rnjak-Kovacina, Y. Lin, and D. L. Kaplan, “pH-dependent anticancer drug release from silk nanoparticles,” Adv. Healthc. Mater. 2(12), 1606–1611 (2013).
[Crossref] [PubMed]

Robinson, E.

E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
[Crossref] [PubMed]

Rockwood, D. N.

D. N. Rockwood, R. C. Preda, T. Yücel, X. Wang, M. L. Lovett, and D. L. Kaplan, “Materials fabrication from Bombyx mori silk fibroin,” Nat. Protoc. 6(10), 1612–1631 (2011).
[Crossref] [PubMed]

Rodrigues, M. O.

I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
[Crossref]

Rodrigues, N. M.

I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
[Crossref]

Rodriguez-Cabezas, M. E.

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

Rodriguez-Nogales, A.

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

Sakakibara, T.

T. Sakakibara, H. K. Fangn Chen, K. Kunieda, R. E. Cuenca, A. F. J. Martin, and R. B. Bankert, “Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts,” Cancer Res. 56, 3743 (1996).

Schäfer, U.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Schaffer, D.

E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
[Crossref] [PubMed]

Schiffelers, R. M.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Sebrie, C.

P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
[Crossref] [PubMed]

Seib, F. P.

F. P. Seib, G. T. Jones, J. Rnjak-Kovacina, Y. Lin, and D. L. Kaplan, “pH-dependent anticancer drug release from silk nanoparticles,” Adv. Healthc. Mater. 2(12), 1606–1611 (2013).
[Crossref] [PubMed]

F. P. Seib and D. L. Kaplan, “Silk for drug delivery applications: opportunities and challenges,” Isr. J. Chem. 53, 756–766 (2013).

F. P. Seib, E. M. Pritchard, and D. L. Kaplan, “Self-assembling doxorubicin silk hydrogels for the focal treatment of primary breast cancer,” Adv. Funct. Mater. 23(1), 58–65 (2013).
[Crossref] [PubMed]

F. P. Seib and D. L. Kaplan, “Doxorubicin-loaded silk films: Drug-silk interactions and in vivo performance in human orthotopic breast cancer,” Biomaterials 33(33), 8442–8450 (2012).
[Crossref] [PubMed]

Seki, T.

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Serre, C.

P. Horcajada, T. Chalati, C. Serre, B. Gillet, C. Sebrie, T. Baati, J. F. Eubank, D. Heurtaux, P. Clayette, C. Kreuz, J.-S. Chang, Y. K. Hwang, V. Marsaud, P.-N. Bories, L. Cynober, S. Gil, G. Férey, P. Couvreur, and R. Gref, “Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging,” Nat. Mater. 9(2), 172–178 (2010).
[Crossref] [PubMed]

Shenderova, O.

V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
[Crossref] [PubMed]

Shiro, T.

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Silva, T. G.

I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
[Crossref]

Simpson, D. A.

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

Sivak, J. G.

H.-Y. Youn, D. J. McCanna, J. G. Sivak, and L. W. Jones, “In vitro ultraviolet-induced damage in human corneal, lens, and retinal pigment epithelial cells,” Mol. Vis. 17, 237–246 (2011).
[PubMed]

Soares, T. A.

I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
[Crossref]

Sougawa, M.

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Storm, G.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Su, L.-J.

Y. Y. Hui, L.-J. Su, O. Y. Chen, Y.-T. Chen, T.-M. Liu, and H.-C. Chang, “Wide-field imaging and flow cytometric analysis of cancer cells in blood by fluorescent nanodiamond labeling and time gating,” Sci. Rep. 4, 5574 (2014).
[Crossref] [PubMed]

Takeuchi, H.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Talelli, M.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Tao, H.

Tirelli, N.

D. Missirlis, R. Kawamura, N. Tirelli, and J. A. Hubbell, “Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles,” Eur. J. Pharm. Sci. 29(2), 120–129 (2006).
[Crossref] [PubMed]

Tomljenovic-Hanic, S.

A. Khalid, K. Chung, R. Rajasekharan, D. W. M. Lau, T. J. Karle, B. C. Gibson, and S. Tomljenovic-Hanic, “Lifetime Reduction and Enhanced Emission of Single Photon Color Centers in Nanodiamond via Surrounding Refractive Index Modification,” Sci. Rep. 5, 11179 (2015).
[Crossref] [PubMed]

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

A. Khalid, R. Lodin, P. Domachuk, H. Tao, J. E. Moreau, D. L. Kaplan, F. G. Omenetto, B. C. Gibson, and S. Tomljenovic-Hanic, “Synthesis and characterization of biocompatible nanodiamond-silk hybrid material,” Biomed. Opt. Express 5(2), 596–608 (2014).
[Crossref] [PubMed]

Tran, P. A.

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

Tsai, N.

V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
[Crossref] [PubMed]

Ubrich, N.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Ulbrich, K.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Utrilla, M. P.

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

Vaijayanthimala, V.

V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
[Crossref] [PubMed]

van Nostrum, C. F.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Varkouhi, A. K.

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

Vasconcelos, I. B.

I. B. Vasconcelos, T. G. Silva, G. C. G. Militao, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. Costa, R. O. Freire, and S. A. Junior, “Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8,” RSC Adv. 2(25), 9437–9442 (2012).
[Crossref]

Volloch, V.

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
[Crossref] [PubMed]

Wakabayashi, M.

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Wang, X.

D. N. Rockwood, R. C. Preda, T. Yücel, X. Wang, M. L. Lovett, and D. L. Kaplan, “Materials fabrication from Bombyx mori silk fibroin,” Nat. Protoc. 6(10), 1612–1631 (2011).
[Crossref] [PubMed]

X. Wang, T. Yucel, Q. Lu, X. Hu, and D. L. Kaplan, “Silk nanospheres and microspheres from silk/pva blend films for drug delivery,” Biomaterials 31(6), 1025–1035 (2010).
[Crossref] [PubMed]

X. Wang, E. Wenk, A. Matsumoto, L. Meinel, C. Li, and D. L. Kaplan, “Silk microspheres for encapsulation and controlled release,” J. Control. Release 117(3), 360–370 (2007).
[Crossref] [PubMed]

Wang, Y.

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
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Wenk, E.

E. Wenk, H. P. Merkle, and L. Meinel, “Silk fibroin as a vehicle for drug delivery applications,” J. Control. Release 150(2), 128–141 (2011).
[Crossref] [PubMed]

X. Wang, E. Wenk, A. Matsumoto, L. Meinel, C. Li, and D. L. Kaplan, “Silk microspheres for encapsulation and controlled release,” J. Control. Release 117(3), 360–370 (2007).
[Crossref] [PubMed]

Yamamoto, H.

A. Lamprecht, N. Ubrich, H. Yamamoto, U. Schäfer, H. Takeuchi, P. Maincent, Y. Kawashima, and C. M. Lehr, “Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease,” J. Pharmacol. Exp. Ther. 299(2), 775–781 (2001).
[PubMed]

Yang, S.

J. Liu, M. Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng, “Passive Tumor Targeting of Renal-Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance,” J. Am. Chem. Soc. 135(13), 4978–4981 (2013).
[Crossref] [PubMed]

Yen, A.

V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H. C. Chang, and O. Shenderova, “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert Opin. Drug Deliv. 12(5), 735–749 (2015).
[Crossref] [PubMed]

Youn, H.-Y.

H.-Y. Youn, D. J. McCanna, J. G. Sivak, and L. W. Jones, “In vitro ultraviolet-induced damage in human corneal, lens, and retinal pigment epithelial cells,” Mol. Vis. 17, 237–246 (2011).
[PubMed]

Yu, M.

J. Liu, M. Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng, “Passive Tumor Targeting of Renal-Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance,” J. Am. Chem. Soc. 135(13), 4978–4981 (2013).
[Crossref] [PubMed]

Yucel, T.

X. Wang, T. Yucel, Q. Lu, X. Hu, and D. L. Kaplan, “Silk nanospheres and microspheres from silk/pva blend films for drug delivery,” Biomaterials 31(6), 1025–1035 (2010).
[Crossref] [PubMed]

Yücel, T.

D. N. Rockwood, R. C. Preda, T. Yücel, X. Wang, M. L. Lovett, and D. L. Kaplan, “Materials fabrication from Bombyx mori silk fibroin,” Nat. Protoc. 6(10), 1612–1631 (2011).
[Crossref] [PubMed]

Yusuf, S. W.

A. M. Rahman, S. W. Yusuf, and M. S. Ewer, “Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation,” Int. J. Nanomedicine 2(4), 567–583 (2007).
[PubMed]

Zeng, X.

X. Zeng, R. Morgenstern, and A. M. Nyström, “Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-mediated drug resistance,” Biomaterials 35(4), 1227–1239 (2014).
[Crossref] [PubMed]

Zhang, X. Q.

E. K. Chow, X. Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).
[Crossref] [PubMed]

Zheng, J.

J. Liu, M. Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng, “Passive Tumor Targeting of Renal-Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance,” J. Am. Chem. Soc. 135(13), 4978–4981 (2013).
[Crossref] [PubMed]

Zhou, C.

J. Liu, M. Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng, “Passive Tumor Targeting of Renal-Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance,” J. Am. Chem. Soc. 135(13), 4978–4981 (2013).
[Crossref] [PubMed]

Zorrilla, P.

A. A. Lozano-Pérez, A. Rodriguez-Nogales, V. Ortiz-Cullera, F. Algieri, J. Garrido-Mesa, P. Zorrilla, M. E. Rodriguez-Cabezas, N. Garrido-Mesa, M. P. Utrilla, L. De Matteis, J. M. de la Fuente, J. L. Cenis, and J. Gálvez, “Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats,” Int. J. Nanomedicine 9, 4507–4520 (2014).
[PubMed]

Zurbuchen, M. A.

M. A. Zurbuchen, M. P. Lake, S. A. Kohan, B. Leung, and L.-S. Bouchard, “Nanodiamond Landmarks for Subcellular Multimodal Optical and Electron Imaging,” Sci. Rep. 3, 2668 (2013).
[Crossref] [PubMed]

ACS Biomater. Sci. Eng. (1)

A. Khalid, A. N. Mitropoulos, B. Marelli, D. A. Simpson, P. A. Tran, F. G. Omenetto, and S. Tomljenovic-Hanic, “Fluorescent nanodiamond silk fibroin spheres: advanced nanoscale bioimaging tool,” ACS Biomater. Sci. Eng. 1(11), 1104–1113 (2015).

Acta Biomater. (1)

J. Brown, C.-L. Lu, J. Coburn, and D. L. Kaplan, “Impact of silk biomaterial structure on proteolysis,” Acta Biomater. 11, 212–221 (2015).
[Crossref] [PubMed]

Adv. Funct. Mater. (1)

F. P. Seib, E. M. Pritchard, and D. L. Kaplan, “Self-assembling doxorubicin silk hydrogels for the focal treatment of primary breast cancer,” Adv. Funct. Mater. 23(1), 58–65 (2013).
[Crossref] [PubMed]

Adv. Healthc. Mater. (1)

F. P. Seib, G. T. Jones, J. Rnjak-Kovacina, Y. Lin, and D. L. Kaplan, “pH-dependent anticancer drug release from silk nanoparticles,” Adv. Healthc. Mater. 2(12), 1606–1611 (2013).
[Crossref] [PubMed]

Adv. Mater. (2)

H. Tao, D. L. Kaplan, and F. G. Omenetto, “Silk Materials - A Road to Sustainable High Technology,” Adv. Mater. 24(21), 2824–2837 (2012).
[Crossref] [PubMed]

A. N. Mitropoulos, G. Perotto, S. Kim, B. Marelli, D. L. Kaplan, and F. G. Omenetto, “Synthesis of silk fibroin micro- and submicron spheres using a co-flow capillary device,” Adv. Mater. 26(7), 1105–1110 (2014).
[Crossref] [PubMed]

Analyst (Lond.) (1)

A. S. Barnard, “Diamond standard in diagnostics: nanodiamond biolabels make their mark,” Analyst (Lond.) 134(9), 1751–1764 (2009).
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Biomacromolecules (1)

A. Florczak, A. Mackiewicz, and H. Dams-Kozlowska, “Functionalized spider silk spheres as drug carriers for targeted cancer therapy,” Biomacromolecules 15(8), 2971–2981 (2014).
[Crossref] [PubMed]

Biomaterials (6)

M. Talelli, M. Iman, A. K. Varkouhi, C. J. Rijcken, R. M. Schiffelers, T. Etrych, K. Ulbrich, C. F. van Nostrum, T. Lammers, G. Storm, and W. E. Hennink, “Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin,” Biomaterials 31(30), 7797–7804 (2010).
[Crossref] [PubMed]

G. H. Altman, F. Diaz, C. Jakuba, T. Calabro, R. L. Horan, J. Chen, H. Lu, J. Richmond, and D. L. Kaplan, “Silk-based biomaterials,” Biomaterials 24(3), 401–416 (2003).
[Crossref] [PubMed]

X. Zeng, R. Morgenstern, and A. M. Nyström, “Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-mediated drug resistance,” Biomaterials 35(4), 1227–1239 (2014).
[Crossref] [PubMed]

R. L. Horan, K. Antle, A. L. Collette, Y. Wang, J. Huang, J. E. Moreau, V. Volloch, D. L. Kaplan, and G. H. Altman, “In vitro degradation of silk fibroin,” Biomaterials 26(17), 3385–3393 (2005).
[Crossref] [PubMed]

X. Wang, T. Yucel, Q. Lu, X. Hu, and D. L. Kaplan, “Silk nanospheres and microspheres from silk/pva blend films for drug delivery,” Biomaterials 31(6), 1025–1035 (2010).
[Crossref] [PubMed]

F. P. Seib and D. L. Kaplan, “Doxorubicin-loaded silk films: Drug-silk interactions and in vivo performance in human orthotopic breast cancer,” Biomaterials 33(33), 8442–8450 (2012).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

Br. J. Cancer (1)

K. Kunieda, T. Seki, S. Nakatani, M. Wakabayashi, T. Shiro, K. Inoue, M. Sougawa, R. Kimura, and K. Harada, “Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer,” Br. J. Cancer 67(4), 668–673 (1993).
[Crossref] [PubMed]

Cancer Res. (1)

T. Sakakibara, H. K. Fangn Chen, K. Kunieda, R. E. Cuenca, A. F. J. Martin, and R. B. Bankert, “Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts,” Cancer Res. 56, 3743 (1996).

Cancer Sci. (1)

H. Maeda, “The link between infection and cancer: tumor vasculature, free radicals, and drug delivery to tumors via the EPR effect,” Cancer Sci. 104(7), 779–789 (2013).
[Crossref] [PubMed]

Eur. J. Pharm. Sci. (1)

D. Missirlis, R. Kawamura, N. Tirelli, and J. A. Hubbell, “Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles,” Eur. J. Pharm. Sci. 29(2), 120–129 (2006).
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Expert Opin. Drug Deliv. (1)

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Figures (11)

Fig. 1
Fig. 1 (a), (b) SEM images for NDSX spheres at day 0 before incubation at 37 °C for drug release. The scans were taken at a magnification of 20 k.
Fig. 2
Fig. 2 SEM images of NDSX spheres samples at magnifications of 10 k (left column) and 20 k (right column) on day 1 (a)-(b), day 3 (c)-(d) and magnification of 75 k and 100 k on day 7 (e)-(f).
Fig. 3
Fig. 3 (a) Fluorescence images of NDSX spheres at 8 × magnification before drug release on day 0. (b) Fluorescence scan of NDs alone and (c) DoX-SF spheres at 8 × magnification. The marked regions were used for emission intensity analysis. The brightness scales from a minimum of 0 to a maximum of 256.
Fig. 4
Fig. 4 Emission intensity in arbitrary units versus time plots for (a) NDSX spheres, (b) NDs alone and (c) DoX-SF spheres. The red data represents the background in the images. (d) Emission from DoX only dropcast on coverslip, showing rapidly photobleaching intensity.
Fig. 5
Fig. 5 Fluorescence images of NDSX spheres (suspended in PBS) drop cast on glass coverslip at 4 × magnification during drug release on (a) day 1, (b) day 3 and (c) day 7. The marked regions were used for emission intensity analysis. The brightness scales from a minimum of 0 to a maximum of 256.
Fig. 6
Fig. 6 Emission intensity (in arbitrary units) plots for NDSX spheres in PBS during drug release on (a) day 1, (b) day 3 and (c) day 7. The intensity of the dark region in the background is shown with red connected dots.
Fig. 7
Fig. 7 Fluorescence images of NDSX spheres (suspended in pro 0.1) drop cast on glass coverslips at 4 × magnification during drug release on (a) day 1, (b) day 3 and (c) day 7. The marked regions were used for emission intensity analysis. The brightness scales from a minimum of 0 to a maximum of 256.
Fig. 8
Fig. 8 Emission intensities (in arbitrary units) for NDSX spheres in pro 0.1 during drug release on (a) day 1, (b) day 3 and (c) day 7. The intensity of the dark region in the background is shown with red connected dots.
Fig. 9
Fig. 9 (a) DoX release percentage from NDSX spheres suspended in PBS (blue) and water (red) at 37°C. (b) Percentage of released DoX from spheres in pro 0.1 (magenta), pro 1 (green) and pro 10 (black) data points. A semi-empirical power law (in respective colours) of Eq. (1) was fitted to the data points for all five solutions in (a)-(b).
Fig. 10
Fig. 10 Snapshots of DoX release from NDSX spheres on day (a) 1, (b) 3, (c) 5 and (c) 7. Cuvettes with sphere suspensions from left to right contain water, PBS, pro 0.1, pro 1 and pro 10 respectively as solvents.
Fig. 11
Fig. 11 Amount of DoX released per day in water (blue), PBS (green), pro 0.1 (black), pro 1 (red) and pro 10 (magenta). Slow and rapid burst effects can also be noticed for respective solvents.

Tables (2)

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Table 1 Emission enhancement for NDs inside SF spheres with respect to bare NDs.

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Table 2 Release kinetics of DoX from NDSX spheres suspended in water, PBS, pro 0.1, pro 1 and pro 10.

Equations (1)

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C t C tot =  C b C tot +k t n ,

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