Synthesis and self-assembly of an acid/reduction co-triggered degradable amphiphilic copolyprodrug as a tumor-selective drug self-delivery system.

Polyprodrugs with drugs as the structural units have been recognized as promising drug self-delivery systems (DSDSs) for tumor chemotherapy, especially ones in which the drug structural units are linked with both pH- and reduction-cleavable conjugations. However, stable DOX derivatives are released after the acid/reduction co-triggered degradation, exhibiting low antitumor efficacy due to their low solubility. Herein, a novel acid/reduction co-triggered degradable amphiphilic copolyprodrug was designed via the facile polycondensation of an acid-labile dimer (D-DOX ADH ) and disulfide-containing monomer (DNC) with a PEGylated dimer (D-DOX ADH -PEG) as an end-capping reagent. The resultant amphiphilic copolyprodrug (PDOX SS-ADH -PEG) with a high DOX content of 61.1% could easily self-assemble into nanoparticles around 154 nm in size, possessing excellent acid/reduction co-triggered DOX release and enhanced inhibition of tumor growth compared to free DOX towards HepG2 cells but showed good cytocompatibility towards L02 cells.