A pH-responsive nanocarrier synergistically activate tumor immunotherapy by promoting pyroptosis and immune checkpoint blocking

Abstract

Tumor immunotherapy has developed rapidly in recent years, with good curative effects and minimal side effects, but it is restricted by the poor tumor immunogenicity. Metformin, a clinical drug used worldwide, has been found to have a novel role in inducing tumor pyroptosis, which in turn promotes tumor to releases inflammatory substances and improve tumor immunogenicity. Nevertheless, it requires a higher dosage for cancer treatment compared to conventional chemotherapy medications, thereby exhibiting pronounced side effects. Within the context of this specific study, we developed a pH-responsive nanocarrier (MT NPs) that can simultaneously deliver metformin as a pyroptosis inducer and Toripalimab as an anti-programmed cell death (PD)-1 monoclonal antibody for the purpose of cancer immunotherapy. Once the nanodrugs reached the acidic tumor microenvironment, their structures were degraded due to hydrophilic transformation caused by segment protonation. Furthermore, the MT NPs released the metformin and Toripalimab to synergistically promote tumor immunity, resulting in significantly improved therapeutic outcomes, potentially leading to successful tumor eradication.