Programmed Catalytic Therapy and Antigen Capture‐Mediated Dendritic Cells Harnessing Cancer Immunotherapies by In Situ‐Forming Adhesive Nanoreservoirs
Bhanu Nirosha Yalamandala, Thi My Hue Huynh, Min‐Ren Chiang, Wei‐Han Weng, Chien‐Wen Chang, Wen‐Hsuan Chiang, Shang‐Hsiu Hu
Abstract
Abstract T lymphocyte recruitment and infiltration promises to suppress the most devastating metastatic tumors for immunotherapy. However, the immune privilege and low vaccine immunogenicity usually reduces the presence of lymphocytes in tumors, especially for invading metastatic clusters. Here, an adhesive catalytic nanoreservoir (CN) containing manganese dioxide (MnO 2 ) and catechol‐functionalized magnetic metal organic framework for the antigens capture and delivery is reported. The intravenously injected CN accumulates at tumor via the marginated target and in situ forming gel for antigen capture. At tumor site, CN releases Mn 2+ for redox reactions by depleting glutathione (GSH) and Fenton‐like activity, i.e., chemodynamic therapy (CDT). Accompanying with hyperthermia, CDT promote the tumor to release the tumor‐associated antigens including neoantigens and damage‐associated molecular patterns. Then, the gels with catechol groups act as antigen reservoirs and deliver the autologous tumor‐associated antigens to dendritic cells, achieving sustained immune stimulation. The in situ‐forming catalytic nanoreservoir at lung metastasis as a magnetothermal‐induced antigen reservoir effectively inhibited the tumor in 60 days and increased the survival rate.