A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug

De-Chao Yang; Xiao-Zhen Yang; Cheng-Miao Luo; Lin-Feng Wen; Jian-Yong Liu; Zhonghui Lin

doi:10.1016/j.ejmech.2022.114749

A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug

Eur J Med Chem. 2022 Dec 5:243:114749. doi: 10.1016/j.ejmech.2022.114749. Epub 2022 Sep 9.

Authors

De-Chao Yang¹, Xiao-Zhen Yang¹, Cheng-Miao Luo¹, Lin-Feng Wen¹, Jian-Yong Liu², Zhonghui Lin¹

Affiliations

¹ National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
² National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, College of Chemistry, Fuzhou University, Fuzhou, 350108, China; Key Laboratory of Molecule Synthesis and Function Discovery, Fujian Province University, College of Chemistry, Fuzhou University, Fuzhou, 350108, China; State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China. Electronic address: lkw82@fzu.edu.cn.

PMID: 36115207
DOI: 10.1016/j.ejmech.2022.114749

Abstract

Herein, we fabricate a multifunctional molecular prodrug BAC where the chemotherapeutical agent camptothecin (CPT) is linked with a boron dipyrromethene (BODIPY)-based photosensitizer by an azobenzene chain which is sensitive to over-expressed azoreductase in hypoxic tumor cells. This prodrug was further loaded into biodegradable monomethoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) to improve its solubility and tumor accumulation. The formed BAC nanoparticles (BAC NPs) can destroy aerobic tumor cells with relatively short distance from blood vessels by photodynamic therapy (PDT) under illumination. The PDT action inevitably leads to consumption of O₂, and subsequently acute hypoxia which can induce cleavage of azobenzene linkage to boost release of CPT killing the other hypoxic interior tumor cells survived from PDT. Both in vitro and in vivo studies have verified that BAC NPs possess remarkable antitumor activity by a synergistic action of PDT and chemotherapy.

Keywords: BODIPY; Hypoxia-activated; Photodynamic therapy; Prodrug; Synergetic therapy.

MeSH terms

Camptothecin / therapeutic use
Cell Line, Tumor
Humans
Hypoxia / drug therapy
Nanoparticles*
Neoplasms* / drug therapy
Photochemotherapy*
Photosensitizing Agents / pharmacology
Photosensitizing Agents / therapeutic use
Prodrugs* / pharmacology
Prodrugs* / therapeutic use

Substances

azobenzene
Camptothecin
methoxy poly(ethylene glycol-co-epsilon-caprolactone)
Photosensitizing Agents
Prodrugs
monomethoxy poly(ethylene glycol)-b-poly(caprolactone)