摘要
Numerous efforts have been devoted to altering the dynamic covalent linkers between the drug structural units in polyprodrugs from the viewpoint of molecular structure;however,the effect of their aggregation states has not yet been explored.Here,the effect of aggregation states on the in vitro drug release and cytotoxicity was investigated using a pH/glutathione(GSH)co-triggered degradable doxorubicin(DOX)-based polyprodrug(PDOX)as a model,which was synthesized by the facile polymerization of a pH/GSH dual-triggered dimeric prodrug(DDOX_(ss))and 2,2-dimethoxypropane(DMP)by forming acid-labile ketal bond.Owing to the pH/GSH dual-triggered disulfide/α-amide and acid-labile ketal linkers between the DOX structural units,the resultant PDOX exhibited excellent pH/GSH co-triggered DOX release.With a similar diameter,the PDOX-NPs1 nanomedicines via fast precipitation showed faster DOX release than PDOX-NPs2 via slow self-assembly,regardless of their polymerization degree(DP).The effect of aggregation states is expected to be a secondary strategy for a more desired tumor intracellular microenvironment-responsive drug delivery for tumor chemotherapy,in addition to the molecular structures of polyprodrugs as drug self-delivery systems(DSDSs).
