Li Fei, Li Tong, Li Keyang, Meng Meng, Guo Xiaoya, He Shasha, Tian Huayu
State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
Nano Lett. 2024 Jun 7. doi: 10.1021/acs.nanolett.4c01464.
Cancer immunotherapy harnesses the immune system to combat cancer, yet tumors often evade immune surveillance through immunosuppressive cells. Herein, we report an organic semiconducting sono-metallo-detonated immunobomb (SMIB) to spatiotemporally tame immunosuppressive cells in situ. SMIB consists of an amphiphilic semiconducting polymer (SP) with a repeatable thiophene-based Schiff base serving as an iron ion chelator (Fe). SMIB increases sonochemical activity through iron chelation and reduces immunosuppressive cell differentiation with metals and sonochemicals, thereby decreasing the irradiation dose. Upon ultrasound irradiation, SMIB acts as a sono-metallo-detonated immunobomb and inhibits Tregs via the mTOR pathway and M2 macrophage polarization through GPX4 regulation. Ultrasensitized sono-generated reactive oxygen species also promote activation of antigen-presenting cells in deep solid tumors (1 cm), resulting in cytotoxic T cell infiltration and enhanced antitumor efficacy. This platform provides a versatile approach for synergistic sono- and metalloregulation of immunosuppressive cells in situ.
癌症免疫疗法利用免疫系统对抗癌症，但肿瘤常常通过免疫抑制细胞逃避免疫监视。在此，我们报告了一种有机半导体声金属引爆免疫炸弹（SMIB），用于在时空上原位驯服免疫抑制细胞。SMIB由一种两亲性半导体聚合物（SP）组成，该聚合物具有可重复的基于噻吩的席夫碱，用作铁离子螯合剂（Fe）。SMIB通过铁螯合增加声化学活性，并通过金属和声化学物质减少免疫抑制细胞分化，从而降低辐射剂量。在超声照射下，SMIB充当声金属引爆免疫炸弹，通过mTOR途径抑制调节性T细胞，并通过GPX4调节抑制M2巨噬细胞极化。超声敏化的声致活性氧还促进深部实体瘤（1厘米）中抗原呈递细胞的激活，导致细胞毒性T细胞浸润并增强抗肿瘤疗效。该平台为原位协同声控和金属调控免疫抑制细胞提供了一种通用方法。
