Nanomotor-Promoted In Situ Vaccination for Deep-Seated Cancer Immunotherapy

Abstract

In situ tumor vaccination, achieved through the induction of immunogenic cell death (ICD), has the potential to elicit robust antitumor immune responses. However, the limited penetration efficiency of drugs and the various immunosuppressive mechanisms present within cells hinder their development and clinical effectiveness. In this study, we propose a nanomotor (AHC-motor)-promoted in situ vaccination strategy for deep-seated cancer immunotherapy through immunomodulation and efficient extracellular matrix penetration. Specifically, the nanomotor consists of catalase-linked tetrasulfide bond-modified hollow mesoporous silica, with 5-aminolevulinic acid encapsulated within it. These AHC-motors exhibit active movement in the H₂O₂ environment and demonstrate enhanced penetration into deep tumor tissues, thereby improving the cellular uptake efficiency of the ICD inducer. Owing to the profound delivery of the ICD inducer, the fabrication of in situ vaccines and the activation of stimulator of interferon genes (STING) have been successfully accomplished. Importantly, these nanomotors, with adaptable preparation characteristics, are equipped with the capacity to promote the persulfidation of zinc finger proteins, resulting in an increased release of proinflammatory cytokines and facilitating the efficacy of in situ vaccine therapy. With its matrix penetration and immunomodulatory properties, the nanomotor may provide insights into the fabrication of in situ vaccines and the development of robust deep-seated immunotherapy.