A modular ROS-responsive platform co-delivered by 10-hydroxycamptothecin and dexamethasone for cancer treatment

Qingye Meng; Hao Hu; Xiaodong Jing; Ying Sun; Liping Zhou; Yaowei Zhu; Bing Yu; Hailin Cong; Youqing Shen

doi:10.1016/j.jconrel.2021.10.027

A modular ROS-responsive platform co-delivered by 10-hydroxycamptothecin and dexamethasone for cancer treatment

J Control Release. 2021 Dec 10:340:102-113. doi: 10.1016/j.jconrel.2021.10.027. Epub 2021 Oct 28.

Authors

Qingye Meng¹, Hao Hu¹, Xiaodong Jing¹, Ying Sun¹, Liping Zhou¹, Yaowei Zhu¹, Bing Yu², Hailin Cong³, Youqing Shen⁴

Affiliations

¹ Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China.
² Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China; Laboratory for New Fiber Materials and Modern Textile, Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071, China.
³ Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China; Laboratory for New Fiber Materials and Modern Textile, Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071, China. Electronic address: conghailin@yahoo.com.
⁴ Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.

PMID: 34718005
DOI: 10.1016/j.jconrel.2021.10.027

Abstract

Traditional and single treatment strategies are difficult to achieve good results due to tumor resistance and complex mechanisms. Combination therapy through co-delivery systems is one of the methods to improve the effectiveness of cancer treatment. The polyprodrug platform has inherent advantages such as high drug loading and strong stability. Herein, a new reactive oxygen species (ROS)-responsive micelle composed of poly 10-hydroxycamptothecin (pHCPT) and PEG is reported, which loaded dexamethasone (DEX) as synergistic drugs. The micelles collapse in the complex microenvironment of tumor cells to release DEX. The first released DEX can increase the ROS level of tumor cells, thereby facilitating the cleavage of thioketal bonds to release intact HCPT molecules. Meanwhile, DEX can normalize tumor blood vessels, reduce adverse reactions, and further improve the efficacy of HCPT. This co-delivery system shows an ideal tumor suppressive effect in vivo and in vitro. Designing drugs into a modular multi-drug platform and selecting appropriate synergistic drugs according to the treatment plan provides a convenient strategy for future clinical treatment.

Keywords: Chemotherapy; Co-delivery system; Polyprodrug; ROS-responsive; Synergistic treatment.

Publication types

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

MeSH terms

Camptothecin / analogs & derivatives
Cell Line, Tumor
Dexamethasone
Drug Delivery Systems
Drug Liberation
Micelles
Nanoparticles*
Neoplasms* / drug therapy
Reactive Oxygen Species

Substances

Micelles
Reactive Oxygen Species
Dexamethasone
10-hydroxycamptothecin
Camptothecin