Biomimetic intelligent nanoplatform with cascade amplification effect for tumor synergy therapy

Tumor heterogeneity, immune-suppressive microenvironment and the precise killing of tumor cells by drugs are important factors affecting tumor treatment. In this study, an environment-responsive therapeutic nanoplatform based on metal-organic frameworks (FM@IQ/PST&ZIF-8/DOX) is developed. Under near-infrared (NIR) irradiation, it realizes the combined treatment of photothermal/immunotherapy/chemotherapy, compensating for the deficiencies of each single treatment and effectively achieving the cascade effect of tumor treatment. When it enters the blood circulation, the surface-modified erythrocyte cell membrane can disguise itself, effectively avoiding its elimination by body immune system. Moreover, the surface-modified folic acid molecules can specific binding with the folic acid receptors on the surface of tumor cells, increasing the uptake of tumor cells to them and thereby promoting its accumulation in tumor tissues. Under NIR irradiation, it induces apoptosis of tumor cells and releases tumor-associated antigen, effectively solving the problem of poor therapeutic effect caused by tumor heterogeneity. Subsequently, the slightly acidic tumor microenvironment can cause the framework of FM@IQ/PST&ZIF-8/DOX to collapse, achieving the precise release of imiquimod and doxorubicin. In this therapeutic platform, imiquimod, as a small molecule immune modulator, can effectively improve the immunosuppressive microenvironment, stimulate the body's anti-tumor immune response and inhibit the recurrence and metastasis of tumors. Therefore, the novel FM@IQ/PST&ZIF-8/DOX drug delivery system designed in this research can not only achieve controllable and precise drug release, but also improve the immunosuppressive tumor microenvironment. It is expected to become a promising new strategy for tumor treatment and provide corresponding inspiration for the later research and development of environment-responsive drugs.