O-carboxymethyl chitosan based pH/hypoxia-responsive micelles relieve hypoxia and induce ROS in tumor microenvironment

Liqun Jiang; Mi Zhang; Yuting Bai; Feiyan Cui; Cong Zhang; Ziyao Wang; Sujia Si; Ling Yang; Yun Wang; Yudong Zhang; Lei Li; Shuo Liu; Xiangrong Wei; Yan Wang; Ya Xu; Jian Meng

doi:10.1016/j.carbpol.2021.118611

O-carboxymethyl chitosan based pH/hypoxia-responsive micelles relieve hypoxia and induce ROS in tumor microenvironment

Carbohydr Polym. 2022 Jan 1:275:118611. doi: 10.1016/j.carbpol.2021.118611. Epub 2021 Aug 26.

Authors

Liqun Jiang¹, Mi Zhang¹, Yuting Bai², Feiyan Cui², Cong Zhang³, Ziyao Wang¹, Sujia Si¹, Ling Yang¹, Yun Wang¹, Yudong Zhang⁴, Lei Li¹, Shuo Liu¹, Xiangrong Wei¹, Yan Wang¹, Ya Xu¹, Jian Meng⁵

Affiliations

¹ School of Pharmacy, Xuzhou Medical University, China.
² XuZhou Central Hospital, XuZhou Clinical College, Xuzhou Medical University, China; School of Stomatology, Xuzhou Medical University, China.
³ Shanghai Frontier Health Pharmaceutical Technology Co., Ltd, China.
⁴ XuZhou Clinical College, Xuzhou Medical University, China.
⁵ XuZhou Central Hospital, XuZhou Clinical College, Xuzhou Medical University, China; School of Stomatology, Xuzhou Medical University, China. Electronic address: 100002014025@xzhmu.edu.cn.

PMID: 34742454
DOI: 10.1016/j.carbpol.2021.118611

Abstract

The hypoxia in tumor microenvironment (TME) can upregulate the HIF-1α and PD-L1 expression and cause immunosuppression of tumor. In this study, a carboxymethyl chitosan-based pH/hypoxia-responsive and γ-Fe₂O₃/isosorbide dinitrate carrying micelle was designed, and it could catalyze endogenous H₂O₂ to generate oxygen and relieve hypoxia in TME, so as to relieve the overexpression of HIF-1α and PD-L1 in tumor; meanwhile, it could react with H₂O₂ to release ROS via Fenton reaction and induce cytotoxicity in tumor. Along with these multiple effects, this carboxymethyl chitosan-based micelles could provide a comprehensive strategy for tumor treatment.

Keywords: HIF-1α; O-carboxymethyl chitosan based micelles; PD-L1; ROS; Tumor microenvironment; pH/hypoxia responsive.

MeSH terms

Animals
Antineoplastic Agents / pharmacology
B7-H1 Antigen / metabolism
Cell Line, Tumor
Chitosan / analogs & derivatives*
Chitosan / chemistry
Chitosan / pharmacology
Ferric Compounds / chemistry
Ferric Compounds / pharmacology
Humans
Hydrogen Peroxide / metabolism
Hydrogen-Ion Concentration
Hypoxia / drug therapy*
Hypoxia / metabolism
Hypoxia / pathology
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Isosorbide Dinitrate / chemistry
Isosorbide Dinitrate / pharmacology
Male
Mice
Micelles*
Oxygen / metabolism
Reactive Oxygen Species / metabolism*
Tumor Microenvironment / drug effects*

Substances

Antineoplastic Agents
B7-H1 Antigen
CD274 protein, human
Ferric Compounds
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
Micelles
O-carboxymethylchitosan
Reactive Oxygen Species
Chitosan
Hydrogen Peroxide
Isosorbide Dinitrate
Oxygen