CO/chemosensitization/antiangiogenesis synergistic therapy with H2O2-responsive diselenide-containing polymer

Jichun Yang; Shuojiong Pan; Shiqian Gao; Tianyu Li; Huaping Xu

doi:10.1016/j.biomaterials.2021.120721

CO/chemosensitization/antiangiogenesis synergistic therapy with H₂O₂-responsive diselenide-containing polymer

Biomaterials. 2021 Apr:271:120721. doi: 10.1016/j.biomaterials.2021.120721. Epub 2021 Feb 17.

Authors

Jichun Yang¹, Shuojiong Pan², Shiqian Gao¹, Tianyu Li³, Huaping Xu⁴

Affiliations

¹ Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, China; Tsinghua-Peking Joint Center for Life Sciences, Beijing, 100084, China.
² Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, China.
³ Department of Biomedical Engineering, Columbia University, New York, NY, 10032, USA.
⁴ Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, China. Electronic address: xuhuaping@mail.tsinghua.edu.cn.

PMID: 33631653
DOI: 10.1016/j.biomaterials.2021.120721

Abstract

Carbon monoxide (CO) therapy and antiangiogenesis therapy (AAT) are regarded as promising approaches for cancer treatment. However, the poor tumor targeting ability and inevitable side effects prevent their clinical application. In this study, we developed H₂O₂-responsive diselenide-containing micelles that combined CO therapy with chemosensitization therapy and AAT in a single system. Under the interaction of intratumoral H₂O₂, CO and gemcitabine (GEM) were released in situ from the micelles to reduce side effects, and CO significantly sensitized the chemotherapeutic effect of GEM by elevating the level of reactive oxygen species (ROS) in human gastric cancer AGS cells. Furthermore, diselenide bonds in the micelles were oxidized to seleninic acid in organic form, which suppressed the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to realize AAT. This study provides an integrated solution to combine CO therapy with chemosensitization therapy and AAT together with good biocompatibility.

Keywords: Antiangiogenesis; Carbon monoxide; Chemosensitization; Diselenide; Vascular endothelial growth factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Humans
Hydrogen Peroxide*
Matrix Metalloproteinase 2
Micelles
Polymers*
Vascular Endothelial Growth Factor A

Substances

Micelles
Polymers
Vascular Endothelial Growth Factor A
Hydrogen Peroxide
Matrix Metalloproteinase 2