Development of Intelligent Target-cell Selective Release Gold Nanorods for Advanced Cancer Theranostics

Abstract

The rapid development of nanomedicine based theranostics has evolved toward practical clinical solutions The gold nanorod conjugates provide adequate contrast for photoacoustic imaging and enabled photothermal therapy (PTT) to augment anti-cancer chemotherapy would achieve simultaneous diagnostics and therapeutics in one In this study we would like to develop an advanced theranostic platform based on gold nanorods modification The photothemal effect can induce simultaneous drug and heat release to kill tumor cells in synergistic way The as synthesized gold nanorods present surface plasma resonance absorption at 800 nm We then modified poly adenine nucleotides (poly-A) on rods surface for carrier anti-cancer drugs 5-fluorouracil (5FU) and targeting moiety by self-assembly In addition an aptamer originally designed to target lung cancer cell was evaluated for oral cancer cell lines targeting and used in this platform Successful conjugation of poly-A and the aptamer was revealed by spectrophotometric quantification of unbound nucleotides which averaged 87 3 poly-As molecules and 7 4 aptamers per rod The loading capacity of the nanorods for anti-cancer drug 5FU was found to be upwards of 74 4 % The aptamer conjugated gold nanorods still significantly improved oral cancer cell targeting as evidenced by observation with fluorescence microscopy In order to reduce cytotoxicity we add polyethylene glycol (PEG) to replace remaining cetyltrimethylammonium bromide (CTAB) Without 5FU conjugation the carrier rods alone showed favorable biocompatibility while targeting conjugation slightly promoted target cell toxicity Cytotoxicity at 12 and 24 hours revealing significantly improved toxicity to cancer cells with 5FU loaded after 24 hours but not in 12 hours demonstrating the slow release of 5FU and augmentation of overall efficacy under such design The therapeutic effect with addition of NIR exposure showed that PTT significantly decrease cancer cell survival in the targeting group AuNR-ap9r with simultaneous chemotherapy (50% viability) then PTT alone (75% ) AuNR without NIR exposure did not cause cell damage at all These results provide evidence for the synergistic effect of synchronized PTT and chemotherapy with NIR radiation as a trigger The strategy of nanorod theranostics provides an opportunity to integrate targeted photothermal and chemotherapy in one platform with prior molecular imaging validation of targeting efficiency and lesion localization Such technology is anticipated to inspire advancement of oral cancer clinical disease management

Date of Award	2014 Sept 2
Original language	English
Supervisor	Dar-Bin Shieh (Supervisor)