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In vivo receptor mediated near‐infrared transferrin uptake using fluorescence lifetime fret: implications in the targeted drug delivery (58.9)
Author(s) -
Rajoria Shilpi,
Zhao Lingling,
Intes Xavier,
Barroso Margarida
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.58.9
Subject(s) - in vivo , förster resonance energy transfer , internalization , transferrin receptor , transferrin , drug delivery , fluorescence lifetime imaging microscopy , cancer research , targeted therapy , photothermal therapy , preclinical imaging , targeted drug delivery , cancer , chemistry , drug , pharmacology , medicine , receptor , fluorescence , nanotechnology , biology , biochemistry , materials science , physics , microbiology and biotechnology , organic chemistry , quantum mechanics
Traditional cancer therapy generally leads to harmful side effects, thus warranting development of targeted therapies which are better tolerated by cancer patients. The main objective of current study is to develop unique in vivo non‐invasive optical imaging assays for the optimization of targeted therapy and diagnostic tools. We propose to quantify the internalization of therapeutic drugs conjugated to transferrin (Tfn), the native ligand of transferrin receptor (TfnR) using a Förster Resonance Energy Transfer (FRET) based imaging technology in vivo. Quantification of in vivo FRET donor % (FD%) in tumor xenografts, indicates a higher proportion of FD% with increasing acceptor:donor ratio demonstrating tumor uptake of NIR‐Tfn. Immunohistochemistry analysis of tumors suggests that the injected NIR‐Tfn is translocated to the tumor site. In conclusion, our novel NIR FRET assay successfully demonstrates a quantitative receptor‐mediated uptake of Tfn in human breast tumors in vivo, allowing for the development of Tfn‐based targeted therapy by means of not only delivering the drug at target site but also potentially block the iron‐internalization function of TfnR, thus directly killing the cancer cell. More importantly, our data supports the quantitative accuracy and sensitivity of a novel NIR FLIM FRET imaging assay to be used non‐invasively through living tissues in a small animal model. Grant Funding Source : National Institutes of Health grant R21 CA161782‐01