Citation: Jiayi Sun, Luyao Huang, Wenfeng Jia, Yitong Liu, Li Xiang, Xing Yang, Fan Tong, Xiaobo Wang, Huile Gao, Yi Zhang. Nanodelivery strategies modulating tumor stromal cells for reverting the immunosuppressive tumor microenvironment[J]. Chinese Chemical Letters, ;2026, 37(4): 112036. doi: 10.1016/j.cclet.2025.112036 shu

Nanodelivery strategies modulating tumor stromal cells for reverting the immunosuppressive tumor microenvironment

Jiayi Sun ^{a, 1} ,
Luyao Huang ^{b, 1} ,
Wenfeng Jia ^c ,
Yitong Liu ^d ,
Li Xiang ^a ,
Xing Yang ^a ,
Fan Tong ^c ,
Xiaobo Wang ^{a, *,} ,
Huile Gao ^{c, *,} ,
Yi Zhang ^{a, *,}

a.
Innovative Institute of Chinese Medicine and Pharmacy/Institute of Interdisciplinary Studies, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
b.
Department of Pharmacy, Hospital of Chengdu Office of People’s Government of Xizang Autonomous Region (Hospital.C.X.), Chengdu 610041, China
c.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Key Laboratory of Leather Chemistry and Engineering (Ministry of Education), West China School of Pharmacy, Sichuan University, Chengdu 610041, China
d.
The Third Affiliated Hospital of Chengdu University of TCM/Chengdu Pidu District Hospital of Traditional Chinese medicine, Chengdu 611730, China

VitaDrwang@cdutcm.edu.cn

gaohuile@scu.edu.cn

zhangyi@cdutcm.edu.cn

Received Date: 11 August 2025
Revised Date: 28 October 2025
Accepted Date: 29 October 2025
Available Online: 30 October 2025

Figures(6)

In contrast to conventional cancer treatment modalities, cancer immunotherapy has increasingly emerged as one of the most promising therapeutic approaches for cancer, owing to its capacity to elicit long-lasting immune memory and its favorable safety profile. However, the immunosuppressive tumor microenvironment (ITME) significantly hinders its progression. While tumor stromal cells play a crucial role in the formation of the ITME, they also offer several potential targets for interventions aimed at reshaping this suppressive milieu. In clinical practice, the modulating of tumor stromal cells overcomes resistance mechanisms, exhibits broader therapeutic potential, and allows for more manageable toxicity profiles. Owing to the capacity of nanodrug delivery systems (nano-DDS) to facilitate accurate targeting and integrate multiple functions, a growing number of researchers are employing nano-DDS in the immunotherapy modulated to tumor stromal cells. This review begins by elucidating the roles played by different tumor stromal cells in the formation of the ITME. Subsequently, we provide the nanodelivery strategies modulating distinct tumor stromal cells. Finally, we propose the current challenges and discuss potential future development directions in this field.
- Nanodrug delivery systems,
- Cancer immunotherapy,
- Tumor-associated macrophages,
- Myeloid-derived suppressor cells,
- Cancer-associated fibroblasts,
- Regulatory T cells
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沈阳化工大学材料科学与工程学院沈阳 110142