Nitric oxide as an all-rounder for enhanced photodynamic therapy: Hypoxia relief, glutathione depletion and reactive nitrogen species generation

Yongyan Deng; Fan Jia; Shengyu Chen; Zhida Shen; Qiao Jin; Guosheng Fu; Jian Ji

doi:10.1016/j.biomaterials.2018.09.043

Nitric oxide as an all-rounder for enhanced photodynamic therapy: Hypoxia relief, glutathione depletion and reactive nitrogen species generation

Biomaterials. 2018 Dec:187:55-65. doi: 10.1016/j.biomaterials.2018.09.043. Epub 2018 Sep 29.

Authors

Yongyan Deng¹, Fan Jia¹, Shengyu Chen², Zhida Shen², Qiao Jin³, Guosheng Fu², Jian Ji⁴

Affiliations

¹ MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang Province, PR China.
² Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, PR China.
³ MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang Province, PR China. Electronic address: jinqiao@zju.edu.cn.
⁴ MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang Province, PR China. Electronic address: jijian@zju.edu.cn.

PMID: 30292942
DOI: 10.1016/j.biomaterials.2018.09.043

Abstract

A glutathione (GSH)-sensitive supramolecular nitric oxide (NO) nanogenerator is developed as an all-rounder for enhanced photodynamic therapy (PDT). By integrating GSH-sensitive NO prodrug into the system via LEGO-like host-guest interaction, the nanocarrier could not only deplete intracellular GSH, but also relieve hypoxia at tumor sites through NO mediated blood vessel relaxation. Furthermore, reactive nitrogen species (RNS) with enhanced biocidal activity could be produced by the reaction between NO and reactive oxygen species (ROS), generated from α-cyclodextrin (α-CD) conjugated S-nitrosothiol and light-activated chlorin e6 (Ce6) respectively. Due to multiple combined effects between NO and PDT, the NO acts as the loaded gunpowder inside a 'grenade', 'explosively' amplifying the therapeutic effects that the light responsive 'fuse' Ce6 could exert. The present work may well serve as an inspiration for future creative approaches of photodynamic cancer therapy.

Keywords: Glutathione depletion; Hypoxia relief; Nitric oxide; Reactive nitrogen species; Reactive oxygen species.

Publication types

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

MeSH terms

Animals
Cell Hypoxia
Cell Survival
Chlorophyllides
Cyclodextrins / chemistry
Drug Carriers
Female
Glutathione / metabolism*
Humans
Light
MCF-7 Cells
Mice, Inbred BALB C
Mice, Nude
Nanoparticles
Nitric Oxide / metabolism*
Photochemotherapy / methods*
Polymers
Porphyrins / chemistry
Reactive Nitrogen Species / metabolism*
Reactive Oxygen Species / metabolism
S-Nitrosothiols / chemistry

Substances

Chlorophyllides
Cyclodextrins
Drug Carriers
Polymers
Porphyrins
Reactive Nitrogen Species
Reactive Oxygen Species
S-Nitrosothiols
Nitric Oxide
phytochlorin
Glutathione