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

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

doi:10.1016/j.mtbio.2022.100304

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

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

Authors

Tingting Wang¹, Jia Wang², Hui Jiang², Mengnan Ni², Yifan Zou³, Yanlong Chen³, Ting Wu², Dan Ding⁴, Huae Xu^{2

3}, Xiaolin Li⁵

Affiliations

¹ The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China.
² Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing, 211116, China.
³ The First Clinical School of Nanjing Medical University, Nanjing, 210029, China.
⁴ State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences, Nankai University, Tianjin, 300071, China.
⁵ Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

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.

Keywords: Curcumin; MDSC; Nano-filaments; Self-assemble.