Facile one-pot synthesis of amphiphilic acid/hypoxia co-triggered degradable diblock polyprodrug for tumor selective drug delivery

More precise drug release is expected by conjugating the drug structural units in the polyprodrugs with dynamic covalent bonds responding to different stimuli. Here, amphiphilic acid/hypoxia co-triggered degradable diblock polyprodrug was designed via a facile one-pot method with drug content of 78.6% (1.22 mmol/g) and relatively molecular weight of 2.08 x 10(4), by condensation polymerization of acid-sensitive dimer of doxorubicin (D-DOXADH) with 2-iminothiolane, in presence of PEGylated D-DOXADH as end capping reagent for the PEGylation. Polyprodrug nanoparticles were easily obtained with mean hydrodynamic diameter of 177.6 +/- 8.9 nm via self-assembly, which showed excellent acid/hypoxia co-triggered degradation and drug release performance. The ideal tumor selective cytotoxicity and enhanced antitumor efficacy were revealed with the in vitro cellular experiments. Such features make the proposed amphiphilic acid/hypoxia co-triggered degradable diblock polyprodrug a promising candidate for tumor chemotherapy.

Automated summary

By conjugating drug structural units in polyprodrugs with dynamic covalent bonds for more precise drug release, an amphiphilic acid/hypoxia co-triggered degradable diblock polyprodrug was designed. The polyprodrug showed excellent acid/hypoxia co-triggered degradation and drug release performance, displaying ideal tumor selective cytotoxicity and enhanced antitumor efficacy in vitro cellular experiments.