Stepwise Size Shrinkage Cascade-Activated Supramolecular Prodrug Boosts Antitumor Immunity by Eliciting Pyroptosis.

ABSTRACT: Effective pyroptosis induction is a promising approach to potentiate cancer immunotherapy. However, the actual efficacy of the present pyroptosis inducers can be weakened by successive biological barriers. Here, a cascaded pH-activated supramolecular nanoprodrug (PDNP) with a stepwise size shrinkage property is developed as a pyroptosis inducer to boost antitumor immune response. PDNPs comprise multiple poly(ethylene glycol) (PEG) and doxorubicin (DOX) drug-polymer hybrid repeating blocks conjugated by ultra-pH-sensitive benzoic imine (bzi) and hydrazone (hyd) bonds. The PEG units endow its "stealth" property and ensure sufficient tumor accumulation. A sharp switch in particle size and detachment of PEG shielding can be triggered by the acidic extracellular pH to achieve deep intratumor pe

SUBMITTER: Liang MY 

PROVIDER: S-EPMC9475545 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature