Biomimetic Nanoplatform Loading Type I Aggregation-Induced Emission Photosensitizer and Glutamine Blockade to Regulate Nutrient Partitioning for Enhancing Antitumor Immunotherapy

The intense metabolism of cancer cells leads to hypoxia and lack of crucial nutrients in the tumor micro-environment, which hinders the function of immune cells. We designed a biomimetic immune metabolic nanoplatform, in which a type I aggregation-induced emission photosensitizer and a glutamine antagonist are encapsulated into a cancer cell membrane for achieving specific delivery in vivo. This approach greatly satisfies the glucose and glutamine required by T cells, significantly improves the tumor hypoxic environment, enables the reprogramming of tumor and immune cell metabolism, induces immunogenic cell death, promotes dendritic cell maturation, and effectively inhibits tumor proliferation. Strong tumor-specific immune responses are further triggered, and the tumor immune-suppressing microenvironment is modulated, by decreasing the number of immunosuppressive cells. Moreover, subsequent combination with anti-PD-1 is able to generate strong abscopal effects to prevent tumor distant metastasis and provide long-term immune memory against tumor recurrence.

Automated summary

The biomimetic immune metabolic nanoplatform designed in this study achieves specific delivery by encapsulating an aggregation-induced emission photosensitizer and a glutamine antagonist into a cancer cell membrane. This approach improves the tumor hypoxic environment, induces immunogenic cell death, promotes dendritic cell maturation, inhibits tumor proliferation, triggers tumor-specific immune responses, and prevents tumor metastasis with the combination of anti-PD-1 therapy.