多酚纳米复合物可调节乳酸代谢重编程并激发免疫反应,从而增强癌症治疗效果

IF 15.8 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Zhan Zhang , Xinnan Li , Weiqiang Liu , Guanglei Chen , Jinchi Liu , Qingtian Ma , Pengjie Hou , Lu Liang , Caigang Liu
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引用次数: 0

摘要

癌症乳酸代谢重编程诱导细胞外乳酸和H+水平升高,导致酸性免疫抑制性肿瘤微环境(TEM)。高乳酸水平可能会影响构成抗肿瘤免疫反应的各种细胞的代谢程序,从而限制免疫介导的肿瘤破坏,导致治疗抵抗和不理想的预后。在这里,我们报告了一种负载天然多酚五倍子黄素的金属酚配位型纳米复合物,它能抑制乳酸脱氢酶的功能,减少乳酸的产生,缓解酸性免疫抑制TME。此外,共包裹的天然多酚肉桂酸和合成的 PEG-Ce6 多酚衍生物(作为光敏剂)在激光照射下可诱导免疫原性癌细胞死亡,从而进一步激活免疫系统,促进免疫细胞在肿瘤组织中的募集和浸润。我们证明,这种基于纳米复合物的组合疗法可以重塑TME,并在小鼠乳腺癌模型中激发免疫反应,这为提高耐药乳腺癌的治疗效率提供了一种前景广阔的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Polyphenol nanocomplex modulates lactate metabolic reprogramming and elicits immune responses to enhance cancer therapeutic effect

Cancer lactate metabolic reprogramming induces an elevated level of extracellular lactate and H+, leading to an acidic immunosuppressive tumor microenvironment (TEM). High lactic acid level may affect the metabolic programs of various cells that comprise an antitumor immune response, therefore, restricting immune-mediated tumor destruction, and leading to therapeutic resistance and unsatisfactory prognosis. Here, we report a metal-phenolic coordination-based nanocomplex loaded with a natural polyphenol galloflavin, which inhibits the function of lactate dehydrogenase, reducing the production of lactic acid, and alleviating the acidic immunosuppressive TME. Besides, the co-entrapped natural polyphenol carnosic acid and the synthetic PEG-Ce6 polyphenol derivative (serving as a photosensitizer) could induce immunogenic cancer cell death upon laser irradiation, which further activates immune system and promotes immune cell recruitment and infiltration in tumor tissues. We demonstrated that this nanocomplex-based combinational therapy could reshape the TME and elicit immune responses in a murine breast cancer model, which provides a promising strategy to enhance the therapeutic efficiency of drug-resistant breast cancer.

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来源期刊
Drug Resistance Updates
Drug Resistance Updates 医学-药学
CiteScore
26.20
自引率
11.90%
发文量
32
审稿时长
29 days
期刊介绍: Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research
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