The adoptive transfer therapy of chimeric antigen receptor-T (CAR-T) has shown remarkable efficacy in hematological malignancies. However, the efficacy of CAR-T in treating solid tumors, especially "cold tumors" such as prostate cancer, is significantly limited by the cumbersome in vitro manufacturing process, impaired T cell adaptability, and the immunosuppressive tumor microenvironment that hinders T cell function. We successfully constructed a nanodelivery system based on zeolite pyrrolidone acid ester framework-8 (ZIF-8). This system exhibits high CAR gene encapsulation efficiency, reduces non-specific liver accumulation, can precisely deliver tumor-associated macrophages (TAM), and efficiently achieve intracellular gene transfection, thereby enabling the in situ construction of chimeric antigen receptor macrophages (CAR-M). The co-delivery of IFN-γ and CAR genes not only maintains the specificity of CAR-Ms in killing tumor cells and their phagocytic activity, but also activates adaptive immunity, thereby inducing excellent anti-tumor efficacy. This was demonstrated in a mouse model of prostate cancer, with a tumor growth inhibition rate reaching 95.54%. This strategy provides a promising approach for systemic in vivo editing of CAR-Ms. This study was published in ACS Nano under the title "Hierarchical Zeolitic Imidazolate Framework-8@Au Cluster Nanocarriers for In Situ Chimeric Antigen Receptor Macrophage Programming and Immunotherapy in Prostate Cancer". References:
DOI: 10.1021/acsnano.5c11870