多通道免疫纳米调节剂抑制乳酸代谢和乳酸形状的酸性微环境,根治抗肿瘤免疫抑制。

IF 26.8 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Chao Fang,Qiuxia Peng,Xiaoying Li,Xiao Qu,Zi Qiao,Binxu Yin,Lujia Xiao,Yi Chen,Xiulin Dong,Lulu Cai,Litao Sun,Kun Zhang
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引用次数: 0

摘要

乳酸(LA)本身和LA型酸性肿瘤微环境(TME)被认为是肿瘤免疫抑制的根本原因,目前尚无有效的策略解决这一问题。本研究设计了一种多通道免疫纳米调节剂来抑制酸性TME并使非炎症性巨噬细胞重新极化,从而消除这种癌症免疫抑制的来源,其中氟碳链(FC)修饰的介孔二氧化硅(FM)作为纳米反应器和载体,分别原位合成CaO2和负载R848,然后依次进行脂质体包被、抗cd105修饰和FC介导的O2结合。脂质体外壳和颗粒内FC确保安全的CaO2输送。超声触发的fc结合O2爆发和脂质体破坏增强的CaO2与H+和H2O的反应产生O2。这一过程消耗原有的H+,抑制糖酵解LA的产生,切断酸性TME来源,并消除它们在重塑癌症免疫抑制中的作用,例如,消除向非炎症性M2细胞的极化动力,解决细胞毒性T淋巴细胞和PD1+ T细胞失活的症状和根本原因等。肿瘤免疫抑制的根除促进了肿瘤钙化和肿瘤内H2O2在免疫纳米调节剂中的积累的抗肿瘤效果,特别是在抗cd105介导的主动靶向积累之后。总的来说,这项工作提出了一种根除LA和非炎性巨噬细胞诱导的癌症免疫抑制的解决方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multichannel Immune Nanoregulators Suppress Lactic Acid Metabolism and Lactic Acid-Shaped Acidic Microenvironment to Uproot Anti-Tumor Immunosuppression.
Lactic acid (LA) itself and the LA-shaped acidic tumor microenvironment (TME) are identified as root causes of cancer immunosuppression, and no effective strategies address them. Here a multichannel immune nanoregulator is engineered to dampen acidic TME and repolarize non-inflammatory macrophages to uproot this source of cancer immunosuppression, wherein fluorocarbon chains (FC)-modified mesoporous silica (FM) serves as nanoreactors and carriers to in situ synthesize CaO2 and load R848, respectively, followed by liposome coating, anti-CD105 modification and FC-mediated O2 binding in sequence. Both liposome shell and intraparticle FC ensure safe CaO2 delivery. Ultrasound-triggered FC-binding O2 burst and liposomes-destruction-enhanced CaO2 reactions with H+ and H2O produce O2. This process depletes pre-existing H+ and inhibits glycolysis LA production to cut off acidic TME source, and uproots their actions in reshaping cancer immunosuppression, e.g., removing the polarization impetus toward non-inflammatory M2 ones, addressing both symptoms and root causes of cytotoxic T lymphocytes and PD1+ T cells inactivation, etc. The cancer immunosuppression uprooting encourages the anti-tumor efficacy of cancer calcification and intratumoral H2O2 accumulation in the immune nanoregulators especially after anti-CD105-mediated active targeting accumulation. Collectively, this work presents a solution to uproot LA and non-inflammatory macrophages-induced cancer immunosuppression.
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来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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