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-DOXADH) and disulfide-containing monomer (DNC) with a PEGylated dimer (D-DOXADH-PEG) as an end-capping reagent. The resultant amphiphilic copolyprodrug (PDOXSS-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.

Automated summary

Polyprodrugs with drugs as the structural units are a promising drug self-delivery system for tumor chemotherapy. An acid/reduction co-triggered degradable amphiphilic copolyprodrug was designed, which showed enhanced inhibition of tumor growth and good cytocompatibility.