Citation: Jin Wang, Qingqing Zhang, Yanchen Li, Xiaoyan Pan, Yuanyuan Shan, Jie Zhang. Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy[J]. Chinese Chemical Letters, ;2024, 35(2): 108746. doi: 10.1016/j.cclet.2023.108746 shu

Remodeling the tumor microenvironment by vascular normalization and GSH-depletion for augmenting tumor immunotherapy

Jin Wang ^a ,
Qingqing Zhang ^a ,
Yanchen Li ^a ,
Xiaoyan Pan ^a ,
Yuanyuan Shan ^{b, *,} ,
Jie Zhang ^{a, *,}

a.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi’an 710061, China
b.
Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an 710061, China

yuanssyuan@163.com

zhj8623@mail.xjtu.edu.cn

Received Date: 4 May 2023
Revised Date: 23 June 2023
Accepted Date: 27 June 2023
Available Online: 29 June 2023

Figures(3)

Remodeling tumor microenvironment (TME) is a very promising and effective strategy to enhance the effects of chemotherapy, photodynamic therapy, and immunotherapy. Normalization of tumor vasculature as well as depletion of glutathione (GSH) can improve the TME. Here, we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles (FEUQ Nps) based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer, a GSH depleting agent, and an activated fluorophore. In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment. In addition, it may deplete GSH in cancer cells, thus inducing the production of reactive oxygen species (ROS) and lipid peroxide (LPO) and promoting iron toxicity. It may also lead to endoplasmic stress and release of calmodulin, which activates the immune system. Meanwhile, quenched fluorophores are turned on in the presence of galactosidase (GLU) for tumor-specific labeling. In summary, we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.
- Vascular normalization,
- Tumor microenvironment,
- GSH depletion,
- Ferroptosis,
- Activated immune
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