IR780-loaded zwitterionic polymeric nanoparticles with acidity-induced agglomeration for enhanced tumor retention

The tumor-targeted delivery of near infrared (NIR)-triggered photothermal therapy (PTT) by varied nanocarriers has captured substantial attention. In order to boost the antitumor efficacy of PTT by promoting cellular uptake and tumor retention of PTT-carrying nanoparticles, the surface charge-changeable polymeric nanoparticles comprising poly(lactic-co-glycolic acid) (PLGA) cores covered with zwitterionic diblock copolymers, methoxypoly(ethylene glycol)-b-poly(methacrylic acid-co-histamine methacryamide), mPEG-b-P(MAA-co-HMA), were developed as vehicles of IR780. Due to the acid-triggered protonation of imidazole groups, the resulting positively charged HMA residues tend to form electrostatic complexes with negatively charged MAA residues, thus facilitating the embedding of outer PEG segments into the neutral and gel-like surfaces and thus the formation of inter-particle aggregation. Taking advantage of the weak acidity of tumor extracellular matrix, the IR780-loaded nanoparticles undergoing acidity-elicited dramatic structural transformation showed appreciably enhanced cellular uptake by TRAMP-C1 cells and prolonged tumor retention time.