Injectable Adhesive Hydrogel as Photothermal-Derived Antigen Reservoir for Enhanced Anti-Tumor Immunity

摘要

Low vaccine immunogenicity and tumor heterogenicity greatly limit the therapeutic effect of tumor vaccine. In this study, a novel injectable adhesive hydrogel, based on thermosensitive nanogels containing catechol groups and loaded with in situ-forming MnO2 nanoparticles, is constructed to overcome these issues. The concentrated nanogel dispersion transforms into an adhesive hydrogel in situ after intratumoral injection. The photothermal effect of the loaded MnO2 nanoparticles induces immunogenic cell death to release mass autologous tumor-derived protein antigens under near-infrared irradiation, which act as ideal immune stimulating substances avoiding the problem of tumor heterogenicity and are captured by the in situ-forming adhesive hydrogel. The antigens-captured adhesive hydrogel acts as an "antigen reservoir" and releases these captured antigens to recruit more dendritic cells to stimulate an intensive and lasting anti-tumor immune response mediated by CD8(+) T cells. The primary tumors can be almost completely disappeared within 4 days without relapse, and the growth of the distal tumors and rechallenged tumors are also effectively inhibited by the treatment with the injectable adhesive hydrogel-based photothermal therapy. Therefore, the proposed "antigen reservoir" strategy shows the great potential application as an in situ-forming personalized vaccine to enhancing the cancer immune therapy.