Promoted cellular uptake and intracellular cargo release of ICG/DOX-carrying hybrid polymeric nanoassemblies upon acidity-activated PEG detachment to enhance cancer photothermal/chemo combination therapy

Abstract

Some studies have reported that the PEGylation of nanoparticle-based drug delivery systems could increase drug solubility, prolong systematic circulation time of drug carriers and decrease immunogenicity. Nevertheless, the uptake of these PEGylated nanoparticles by cancer cells was largely hindered. To promote intracellular co-delivery of indocyanine green (ICG), an amphiphilic photothermal transduction agent, and doxorubicin (DOX), a chemotherapy drug, for improved anticancer efficacy of the photothermal/chemo combination therapy, the hybrid polymeric nanoassemblies equipped with acid-activated PEG detachment were developed as vehicles by co-assembly of hydrophobic poly(lactic-co-glycolic acid) (PLGA), pH-responsive methoxy poly(ethylene glycol)-benzoic imine-octadecane (mPEG5k-b-C18) and amphiphilic tocopheryl polyethylene glycol succinate (TPGS) segments in aqueous solution of pH 8.0. The ICG/DOX-carrying mPEG5k-b-C18/TPGS/PLGA nanoassemblies (ID@PbCTPNs) were characterized to exhibit a well-dispersed spherical shape and maintained stable colloidal structure in serum-containing solution. Also ID@PbCTPNs sufficiently reduced ICG self-aggregation and leakage in pH 7.4 aqueous solution, thereby enhancing aqueous photostability and photo-elicited hyperthermia of ICG molecules. With the solution pH being lowered from 7.4 to 5.0, the acid-triggered dePEGylation of ID@PbCTPNs not only led to reduction of particle size but also accelerated cargo liberation. The findings of in vitro cellular uptake and cytotoxicity revealed that the cellular uptake and intracellular drug release of ID@PbCTPNs was appreciably increased via acid-elicited dePEGylation, thus largely promoting their anticancer potency on TRAMP-C1 cells by the photothermal/chemo combinatorial therapy. This work demonstrates that the designed ID@PbCTPNs show the promising application in cancer treatment.