Traditional Chinese medicine-facilitated redox-labile paclitaxel dimer nanoprodrug for efficient chemoimmunotherapy.
10.1016/j.jpha.2025.101348
- Author:
Fan LI
1
;
Wenrui WANG
2
;
Weisheng XU
3
;
WanYing LI
4
;
Yudi LU
4
;
Rui WANG
4
;
Zhonggui HE
5
;
Zhihui FENG
4
;
Jiabing TONG
1
;
Zhenbao LI
4
Author Information
1. The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, China.
2. Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University, Bengbu, Anhui, 233004, China.
3. The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
4. School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.
5. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China.
- Publication Type:Journal Article
- Keywords:
Chemoimmunotherapy;
Immunosuppressive microenvironment;
Lung cancer;
Paclitaxel nanoprodrug;
Qi-Yu-San-long-Fang
- From:
Journal of Pharmaceutical Analysis
2025;15(9):101348-101348
- CountryChina
- Language:English
-
Abstract:
Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H2O2, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4+ T and CD8+ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.
