Precise Engineering of a Se/Te Nanochaperone for Reinvigorating Cancer Radio‐Immunotherapy

Abstract Facilely synthesized nanoradiosensitizers with well‐controlled structure and multifunctionality are greatly desired to address the challenges of cancer radiotherapy. In this work, a universal method is developed for synthesizing chalcogen‐based TeSe nano‐heterojunctions (NHJs) with rod‐, spindle‐, or dumbbell‐like morphologies by engineering the surfactant and added selenite. Interestingly, dumbbell‐shaped TeSe NHJs (TeSe NDs) as chaperone exhibit better radio‐sensitizing activities than the other two nanostructural shapes. Meanwhile, TeSe NDs can serve as cytotoxic chemodrugs that degrade to highly toxic metabolites in acidic environment and deplete GSH within tumor to facilitate radiotherapy. More importantly, the combination of TeSe NDs with radiotherapy significantly decreases regulatory T cells and M2‐phenotype tumor‐associated macrophage infiltrations within tumors to reshape the immunosuppressive microenvironment and induce robust T lymphocytes‐mediated antitumor immunity, resulting in great abscopal effects on combating distant tumor progression. This study provides a universal method for preparing NHJ with well‐controlled structure and developing nanoradiosensitizers to overcome the clinical challenges of cancer radiotherapy.