Indocyanine green-carrying polymeric nanoparticles with acid-triggered detachable PEG coating and drug release for boosting cancer photothermal therapy

In order to boost anticancer efficacy of indocyanine green (ICG)-mediated photothermal therapy (PTT) by promoting intracellular ICG delivery, the ICG-carrying hybrid polymeric nanoparticles were fabricated in this study by co-assembly of hydrophobic poly(lactic-co-glycolic acid) (PLGA) segments, ICG molecules, amphiphilic tocopheryl polyethylene glycol succinate (TPGS) and pH-responsive methoxy poly(ethylene glycol)-benzoic imine-1-octadecanamine (mPEG-b-C18) segments in aqueous solution. The ICG-loaded nanoparticles were characterized to have ICG-containing PLGA core stabilized by hydrophilic PEG-rich surface coating and a well-dispersed spherical shape. Moreover, the ICG-loaded nanoparticles in pH 7.4 aqueous solution sufficiently inhibited ICG self-aggregation and leakage, thereby increasing aqueous photostability of ICG molecules. Notably, when the solution pH was reduced from pH 7.4–5.5, the acid-triggered hydrolysis of benzoic-imine linkers within mPEG-b-C18 remarkably facilitated the detachment of mPEG segments from ICG-loaded nanoparticles, thus accelerating ICG release. The findings of in vitro cellular uptake and cytotoxicity studies further demonstrated that the PEGylated ICG-carrying hybrid nanoparticles were efficiently internalized by MCF-7 cells compared to free ICG and realized intracellular acid-triggered rapid ICG liberation, thus enhancing anticancer effect of ICG-mediated PTT to potently kill cancer cells.