Abstract
Polyprodrugs have attracted more interest in tumor chemotherapy owing to their better on-demand controlled drug release than the conventional polymer prodrugs. Here, pH/reduction dual-triggered crosslinked polyprodrug nanoparticles were designed by the facile polycondensation of hexachlorocyclotriphosphazene (HCCP) and cystamine (Cys) modified DOX (DOX-Cys), with a higher DOX content of 53.41 % and mean hydrodynamic diameter (Dh) of 178.9 nm and narrow distribution. The in vitro drug release and cytotoxicity results indicated that introducing hydrophilic and flexible acid/GSH dual-triggered cleavable spacer in the crosslinked polyprodrug nanoparticles not only endowed the GSH-responsiveness with disulfide bond, but also modulated the acid-triggered drug release with Schiff base bond, making them a promising potential for tumor specific DOX delivery with minimized toxic/side effects, desired tumor selectivity and higher anti-tumor efficacy.
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