Engineering Nanosensitizer to Remodel the TME for Hypoimmunogenic “Cold”–“Hot” Tumor Transformations

作者：Zhongqing Liu, Ziqi Wang, Zhishuai Zhang, Zhenwei Zhang, Xin Qi, Hanwen Zhu, Kuo Zhang, Tianrui Qu, Yubo Zhao, Zhijian Kang, Fanshu Zeng, Pengyu Guo, Zhichao Tong, Lu Wang, Hao Wang, Wanhai Xu · 发表于：Nano Letters · 年份：2024 · DOI：10.1021/acs.nanolett.3c03816 · 被引用次数：8 · 研究领域：Nanoplatforms for cancer theranostics、Cancer Immunotherapy and Biomarkers、Cancer Research and Treatments

α-PD-L1 therapy has shown encouraging results at harnessing the immune system to combat cancer. However, the treatment effect is relatively low due to the dense extracellular matrix (ECM) and tumor immunosuppressive microenvironment (TIME). Therefore, an ultrasound (US)-responsive nanosensitizer (URNS) is engineered to deliver losartan (LST) and polyethylenimine (PEI) to remolde the TME, driving “cold”–“hot” tumor transformation and enhancing the sensitivity of α-PD-L1 therapy. In the tumor site, noninvasive US can make MTNP generate ROS, which cleave ROS-sensitive bonds to dissociate MTNP tK @LST-PEI, shedding PEI and releasing LST from mesoporous spheres. The results demonstrated that URNS combined with α-PD-L1 therapy effectively inhibited tumor growth with an inhibition rate as high as 90%, which was 1.7-fold higher than that of the α-PD-L1 treatment in vivo . In summary, the URNS improves the sensitivity of α-PD-L1 therapy by remodeling the TME, which provides promising insights for optimizing cancer immunotherapy.