Abstract
Polyprodrugs, in which drug was used as the structural unit by linking with each other via the dynamic covalent bonds in the main chain, are expected to endow excellent drug delivery performance. Here, acid-triggered degradable diblock polyprodrug, poly(doxorubicin)-polyethylene glycol (PDOX-PEG), was designed with DOX as structural unit alternately linked with acid-labile hydrazone and maleic amide groups, by the polycondensation of DOX-based dimers (D-DOXADH or D-DOXMAH) with PEGylated dimer (DOX-ADH-DOX-PEG) as end capping agent. The optimized PDOX-PEG, which was synthesized with D-DOXADH and the PEGylated dimer at a feeding ratio of 10%, possessed a high Mn of 3.1 × 104 g/mol with a high DOX content of 75.42%. It could easily self-assemble into near spherical nanoparticles with average hydrodynamic diameter of 135 nm. They showed excellent pH-triggered sustained drug release owing to the acid-triggered degradation of the polyprodrug block in the tumor intracellular microenvironment, with low premature drug leakage of 4.39 % within 60 h. The MTT results indicated the enhanced antitumor efficacy of the proposed PDOX-PEG nanoparticles than free DOX. The results demonstrated the promising potential of the proposed acid-triggered degradable diblock PDOX-PEG polyprodrug for tumor treatment.
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