通过纳米制剂改善缺氧微环境以实现小鼠模型中有效的 T 细胞治疗

The immunostimulatory efficacy of our nanoparticles was evaluated in vitro using DC activation assays and in vivo in an H22 murine hepatocellular carcinoma model. Flow cytometry was employed to assess immune cell populations in tumors and lymph nodes, while immunofluorescence microscopy was used to analyze tumor hypoxia and T cell infiltration.

The oxygen-generating MSN formulation effectively alleviated intratumoral hypoxia, promoted DC maturation (CD80 + CD86 + ), and facilitated effector CD8 + T cell infiltration into tumors. In vivo, co-administration of the nanoformulation with ACT led to enhanced tumor suppression and systemic antitumor immune responses without evident toxicity to major organs.

This oxygen-producing immunomodulatory nanoplatform remodels the immunosuppressive TME and significantly enhances the efficacy of ACT in solid tumors, offering a promising strategy for overcoming current barriers in T cell-based immunotherapy. Adoptive T cell therapy is a promising treatment that uses a person’s own immune cells to fight cancer. However, it does not work well in solid tumors because the tumor environment is often low in oxygen and blocks immune responses. To solve this problem, our research team developed tiny particles, called MSN-R837-MnO 2 /ZnO 2 nanoparticles, that are specially designed to help immune cells work better in tumors. These nanoparticles respond to the acidic conditions found in solid tumors. Once they arrive at the tumor site, they do several important things:They release oxygen to improve the low-oxygen conditions (called hypoxia) inside the tumor.They activate immune cells called dendritic cells (DCs), which help trigger stronger immune attacks. They support the activity of adoptive T cells, which are the key cancer-fighting cells used in this therapy.In tests on mice with liver tumors, we found that these nanoparticles reduced tumor growth, improved oxygen levels in the tumor, and helped immune cells enter and stay active inside the tumor. Mice treated with our approach lived longer and had fewer side effects. This study shows that carefully designed nanoparticles can create a more supportive environment for immune cells in solid tumors. Our work could help make adoptive T cell therapy more effective and safer for people with difficult-to-treat cancers in the future.