One of the challenges in anti-cancer drug delivery systems is to quantitatively discriminate non-specific receptor-independent tumor accumulation from receptor-mediated uptake into the tumor cells. To overcome this challenge, we develop a new near infrared fluorescence resonance energy transfer fluorescence lifetime imaging (NIR FRET FLIM) technique with wide-field illumination strategies to validate and characterize cellular uptake in both cancer cells and normal cells with different donor-acceptor ratios in vitro and in vivo. Our results demonstrate that NIR FRET FLIM can quantitatively distinguish receptor-bound from unbound donor in live animals with high sensitivity and high accuracy. Thus, it has a great potential for the quantitative detection of targeted delivery systems for diagnostic and therapeutic use.

© 2013 SPIE

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