Metal-Phenolic Network-Enabled Lactic Acid Consumption Reverses Immunosuppressive Tumor Microenvironment for Sonodynamic Therapy,ACS Nano

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Metal-Phenolic Network-Enabled Lactic Acid Consumption Reverses Immunosuppressive Tumor Microenvironment for Sonodynamic Therapy
ACS Nano ( IF 15.8 ) Pub Date : 2021-10-18 , DOI: 10.1021/acsnano.1c08026
Zhan Zhang _{1,

2} , Bei Li _{1,

2} , Lisi Xie _{1,

2} , Wei Sang _{1,

2} , Hao Tian _{1,

2} , Jie Li _{1,

2} , Guohao Wang _{1,

2} , Yunlu Dai _{1,

2}

Affiliation

Nanomedicine has revolutionized cancer therapeutic strategies but has not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) such as acidification. Here, a metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and a mitochondrial respiration inhibitor atovaquone (ATO) was constructed for immunosuppressive TME remodeling and sonodynamic therapy (SDT). In this nanocomplex, the sonosensitizer chlorin e6-conjugated polyphenol derivative can induce the generation of tumor lethal reactive oxygen species upon ultrasound irradiation. LOX served as a catalyst for intracellular lactic acid exhaustion, and ATO led to mitochondrial dysfunction to decrease oxygen consumption. This nanocomplex reversed the tumor immunosuppressive status by alleviating tumor hypoxia and acidic TME, achieving the characteristic enhancement of SDT and the inhibition of tumor proliferation and metastasis.

中文翻译：

金属酚类网络启用的乳酸消耗逆转用于声动力学治疗的免疫抑制肿瘤微环境

纳米医学已经彻底改变了癌症治疗策略，但并没有完全改变棘手的肿瘤的结果，这些肿瘤演化出复杂的免疫抑制肿瘤微环境 (TME)，例如酸化。在这里，构建了一种嵌入乳酸氧化酶 (LOX) 和线粒体呼吸抑制剂 atovaquone (ATO) 的基于金属-酚类网络的纳米复合物，用于免疫抑制性 TME 重塑和声动力学治疗 (SDT)。在这种纳米复合物中，声敏剂二氢卟酚 e6 共轭多酚衍生物可以在超声照射下诱导肿瘤致死活性氧的产生。LOX 作为细胞内乳酸耗竭的催化剂，ATO 导致线粒体功能障碍以减少耗氧量。

更新日期：2021-10-26

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