Hollow MnO₂ Nanoparticles Loaded with Functional Genes as Nanovaccines for Synergistic Cancer Therapy

Nanotechnology provides more developments and challenges for cancer immunotherapy. Nanomaterial-mediated synergistic therapy, immunosuppressive adjustment of the tumor microenvironment (TME), and nanovaccine construction can promote cancer immunotherapy. Here, based on the biodegradable hollow manganese dioxide (H-MnO2) tumor-targeted drug delivery platform, we have developed a TME-responsive nanovaccine for synergistic cancer therapy. The nanoplatform significantly enhanced photodynamic therapy (PDT)-mediated immune response by improving the hypoxic tumor microenvironment and on-demand drug release. At the same time, it was supplemented with gene therapy and chemotherapy to achieve significant in vivo combined therapy benefits. Taking full advantage of the high reactivity to the hydrogen peroxide and weak acidity of the TME, H-MnO2 loaded with chemotherapy drug doxorubicin (DOX) and photosensitizer chlorin e6 (Ce6) not only provided the required oxygen for photodynamic therapy but also reduced the side effects of chemotherapy drugs on normal tissues. Moreover, the coating of nucleic acid on H-MnO2 solved the problem of biocompatibility of nanoparticles and ensured that they could be swallowed by cancer cells. The results revealed that through the controlled release of targeted drugs and combined therapy, the synergistic nanovaccine significantly inhibited tumor growth in mice, which is expected to achieve the treatment of primary tumors.