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

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Engineering Nanosensitizer to Remodel the TME for Hypoimmunogenic “Cold”–“Hot” Tumor Transformations
Nano Letters ( IF 9.6 ) Pub Date : 2024-01-29 , DOI: 10.1021/acs.nanolett.3c03816
Zhongqing Liu _{1,

2,

3} , Ziqi Wang _{1,

2,

4} , Zhishuai Zhang _{1,

2,

4} , Zhenwei Zhang _{1,

2,

4} , Xin Qi _{1,

2,

4} , Hanwen Zhu _{1,

2,

4} , Kuo Zhang _{1,

2,

4} , Tianrui Qu _{1,

2} , Yubo Zhao _{1,

2,

4} , Zhijian Kang _{1,

2,

4} , Fanshu Zeng _{1,

2} , Pengyu Guo _{1,

2,

4} , Zhichao Tong _{1,

2} , Lu Wang _{1,

2} , Hao Wang _{1,

5} , Wanhai Xu _{1,

2,

4}

Affiliation

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.

中文翻译：

工程纳米增敏剂重塑 TME 以实现低免疫原性“冷”-“热”肿瘤转化

α-PD-L1 疗法在利用免疫系统对抗癌症方面显示出令人鼓舞的结果。然而，由于致密的细胞外基质（ECM）和肿瘤免疫抑制微环境（TIME），治疗效果相对较低。因此，设计了一种超声（US）响应性纳米增敏剂（URNS）来传递氯沙坦（LST）和聚乙烯亚胺（PEI）来重塑TME，驱动“冷”-“热”肿瘤转化并增强α-PD-的敏感性。 L1疗法。在肿瘤部位，无创超声可以使 MTNP 产生 ROS，从而裂解 ROS 敏感键，解离 MTNP _tK @LST-PEI，脱落 PEI 并从介孔球中释放 LST。结果表明，URNS联合α-PD-L1治疗有效抑制肿瘤生长，抑制率高达90%，体内抑制率是α-PD-L1治疗的1.7倍。总之，URNS 通过重塑 TME 提高了 α-PD-L1 治疗的敏感性，这为优化癌症免疫治疗提供了有希望的见解。

更新日期：2024-01-29

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