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通过负载姜黄素的自组装纳米丝抑制髓源性抑制细胞来靶向调节肿瘤微环境。

Targeted regulation of tumor microenvironment through the inhibition of MDSCs by curcumin loaded self-assembled nano-filaments.

作者信息

Wang Tingting, Wang Jia, Jiang Hui, Ni Mengnan, Zou Yifan, Chen Yanlong, Wu Ting, Ding Dan, Xu Huae, Li Xiaolin

机构信息

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.

Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211116, China.

出版信息

Mater Today Bio. 2022 May 25;15:100304. doi: 10.1016/j.mtbio.2022.100304. eCollection 2022 Jun.

DOI:10.1016/j.mtbio.2022.100304
PMID:35711288
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9194645/
Abstract

One of the most important reasons underlying the resistance of tumors is the immune suppression induced by cancer cells. Myeloid-derived suppressor cells (MDSCs), which exerts pivotal functions in immunosuppression, is a key participator in tumor microenvironment and a novel target for cancer therapy. Here curcumin (Cur) was employed as a specific MDSCs repressor to inhibit the number and function of MDSCs. Moreover, a novel self-assembled nano-filament system was generated through the conjugation of Cur and a self-assembled peptide. study demonstrated the powerful antitumor effect of curcumin-loaded nano-filaments (Nano-Cur) with delayed tumor growth and longer survival. The immune status of tumor microenvironment (TME) was well improved by Nano-Cur treatment with increased T cell proliferation and activation as well as enhanced production of inflammatory mediators such as GM-CSF and IL-6, which revealed that Nano-Cur contributed to relieve the tumor burden by regulating and improving the TME. Furthermore, flow cytometry analysis implied the lower MDSCs levels under Nano-Cur treatment, which indicated that the anticancer effect of Nano-Cur may be associated with the inhibition of recruitment and accumulation of MDSCs in the TME. Therefore, Nano-Cur may be a novel therapeutic approach for lung cancer, and extensive studies of mechanisms are required to better understand how TME affects tumor progression and provide new insights into anticancer therapeutics.

摘要

肿瘤产生耐药性的最重要原因之一是癌细胞诱导的免疫抑制。髓源性抑制细胞(MDSCs)在免疫抑制中发挥关键作用,是肿瘤微环境中的关键参与者和癌症治疗的新靶点。在此,姜黄素(Cur)被用作一种特异性的MDSCs抑制剂,以抑制MDSCs的数量和功能。此外,通过将Cur与一种自组装肽偶联,构建了一种新型的自组装纳米丝系统。研究证明了负载姜黄素的纳米丝(Nano-Cur)具有强大的抗肿瘤作用,可延缓肿瘤生长并延长生存期。Nano-Cur治疗可显著改善肿瘤微环境(TME)的免疫状态,增加T细胞增殖和活化,并增强炎症介质如GM-CSF和IL-6的产生,这表明Nano-Cur通过调节和改善TME有助于减轻肿瘤负担。此外,流式细胞术分析表明Nano-Cur治疗组的MDSCs水平较低,这表明Nano-Cur的抗癌作用可能与抑制TME中MDSCs的募集和积累有关。因此,Nano-Cur可能是一种治疗肺癌的新方法,需要进行广泛的机制研究,以更好地理解TME如何影响肿瘤进展,并为抗癌治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d49/9194645/7036d5a0677d/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d49/9194645/00ac14811000/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d49/9194645/288b24885f36/gr1.jpg
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