ROS-responsive Nanoparticle-mediated Delivery of CYP2J2 Gene for Therapeutic Angiogenesis in Severe Hindlimb Ischemia

Overview

Journal Mater Today Bio

Specialty Biomedical Engineering

Date 2022 Jan 6

PMID 34988419

Citations 4

Authors

Liang Gui

Youlu Chen

Yongpeng Diao

Zuoguan Chen

Jianwei Duan

Xiaoyu Liang

Huiyang Li

Kaijing Liu

Yuqing Miao

Qing Gao

Zhichao Li

Jing Yang

Yongjun Li

Affiliations

Soon will be listed here.

Abstract

With critical limb ischemia (CLI) being a multi-factorial disease, it is becoming evident that gene therapy with a multiple bio-functional growth factor could achieve better therapeutic outcomes. Cytochrome P450 epoxygenase-2J2 (CYP2J2) and its catalytic products epoxyeicosatrienoic acids (EETs) exhibit pleiotropic biological activities, including pro-angiogenic, anti-inflammatory and cardiovascular protective effects, which are considerably beneficial for reversing ischemia and restoring local blood flow in CLI. Here, we designed a nanoparticle-based pcDNA3.1-CYP2J2 plasmid DNA (pDNA) delivery system (nanoparticle/pDNA complex) composed of a novel three-arm star block copolymer (3S-PLGA-po-PEG), which was achieved by conjugating three-armed PLGA to PEG via the peroxalate ester bond. Considering the multiple bio-functions of CYP2J2-EETs and the sensitivity of the peroxalate ester bond to HO, this nanoparticle-based gene delivery system is expected to exhibit excellent pro-angiogenic effects while improving the high oxidative stress and inflammatory micro-environment in ischemic hindlimb. Our study reports the first application of CYP2J2 in the field of therapeutic angiogenesis for CLI treatment and our findings demonstrated good biocompatibility, stability and properties of the CYP2J2 nano-delivery system. In summary, 3S-PLGA-po-PEG/CYP2J2-pDNA complexes have tremendous potential and provide a practical strategy for the treatment of limb ischemia. Moreover, 3S-PLGA-po-PEG nanoparticles might be useful as a potential non-viral carrier for other gene delivery applications.

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