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. (15th January 2022)

• Record Type: Journal Article
• Authors: Hung, Yu-Ning; Liu, Yu-Ling; Chou, Ya-Hsuan; Hu, Shang-Hsiu; Cheng, Bill; Chiang, Wen-Hsuan
• Is Part Of: European polymer journal. Volume 163(2022)
• Publication Date: 2022-01-15
• Subjects: Indocyanine green -- Photothermal/chemo therapy -- Acidity-triggered dePEGylation -- Controlled drug release -- Hybrid polymeric nanoassemblies; Polymers -- Periodicals; Polymerization -- Periodicals; Polymères -- Périodiques; Polymérisation -- Périodiques; Polymerization; Polymers; Periodicals; Electronic journals; 547.705
• DOI: 10.1016/j.eurpolymj.2021.110944
• Languages: English
• ISSNs: 0014-3057

Abstract

Graphical abstract: Highlights: The amphiphilic mPEG5k -b-C18 adducts with acid-labile benzoic-imine bond were synthesized. The ICG/DOX-carrying hybrid nanoassemblies exhibited acid-triggered drug release upon PEG detachment. The dePEGylation of ICG/DOX-carrying nanoassemblies promoted cellular uptake and intracellular cargo liberation. The ICG/DOX-carrying nanoassemblies enhanced cancer photothermal/chemo combinatorial 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.