Oxidation‐Responsive Nanoassemblies for Light‐Enhanced Gene Therapy

Microenvironment‐responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation‐responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via...

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Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2019-11, Vol.15 (45), p.e1904017-n/a
Main Authors: Zhang, Na, Wang, Yu, Wu, Rui, Xu, Chen, Nie, Jing‐Jun, Zhao, Nana, Yu, Bingran, Liu, Zunjin, Xu, Fu‐Jian
Format: Article
Language:English
Subjects:
Anticancer properties
antitumor
Assemblies
assembly
Biomedical materials
Cyclodextrins
Dismantling
Drug delivery systems
Gene therapy
Hydrogen peroxide
In vivo methods and tests
light‐enhanced
Nanotechnology
Oxidation
oxidation‐responsive
Polyelectrolytes
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Summary:Microenvironment‐responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation‐responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host–guest interaction of β‐cyclodextrin based polycations and a ferrocene‐functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H2O2 concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (1O2), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation‐responsive nanoassemblies with light‐enhanced gene transfection performance. Oxidation‐triggered nanoassemblies named CPAs are prepared for high‐performance nucleic acid delivery. CPAs produce enhanced gene transfection efficiency due to their disassembly induced by illumination and H2O2 in the tumor environment, which is utilized for effective gene therapy in 4T1‐based cancer.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.201904017