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

通过姜黄素负载的自组装纳米丝抑制 MDSC 来靶向调节肿瘤微环境

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

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. In vivo 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.

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