Oxidation‐Responsive Nanoassemblies for Light‐Enhanced Gene Therapy

Abstract

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.

Stimuli-responsive cyclodextrin-based supramolecular assemblies as drug carriers

“…3B). 73 The polycation part of the system, star-shaped CD-based ethanolamine-functionalized poly(glycidyl methacrylate)s, was applied to interact with p53 through an electrostatic interaction, and the zinc tetraaminophthalocyanine modified by Fc (TAPc-Fc) served as photosensitizers. In this study, 1 O 2 produced under illumination showed a limited improvement of transfection efficiency in cancer cells with high ROS levels, whereas the transfection efficiency was improved in cancer cells with low ROS levels.…”

“…58,72 As a result, redox differences between normal tissues and abnormal regions contributed to the construction of redoxresponsive assemblies (Table 2). 69,[73][74][75][76][77][78] The overexpression of both ROS (up to 100 mM) and GSH (B10 mM) in tumor cells has been repeatedly highlighted as essential triggers for controlling the intracellular drug release. 26 ROS/GSH sensitive linkers are commonly used in redox-responsive supramolecular assemblies.…”

Multifunctional co-transport carriers based on cyclodextrin assembly for cancer synergistic therapy

“…In particular, the assembly can be decomposed upon exposure to oxidative conditions, which makes it an outstanding candidate for cancer treatment. A previous study reported that nanoparticles assembled by β-CD based polycations and Fc-functionalized zinc tetraaminophthalocyanine (TAPc-Fc) could be used for regulatory gene and photosensitivity synergistic therapy (Figure 5 a) 76 . Reactive oxygen could accelerate the decomposition of the assembly complex, which further promoted the release of p53 gene.…”

“… (A) Assembly process of β-CD based polycations and Fc-functionalized zinc tetraaminophthalocyanine. Adapted with permission from 76 , Copyright 2019 Wiley-VCH. (B) Schematic of multifunctional nanoparticle with imaging, drug therapy, gene therapy and hyperthermia functions.…”

Versatile Types of Cyclodextrin‐Based Nucleic Acid Delivery Systems

“…In order to further extend the application of supramolecular assembly via CD-Fc interaction, we proposed a series of photosensitizer-embedded supramolecular polycationic assemblies (CPAs) with intracellular oxidation responsiveness and irradiation-controlled disassembly (Figure 6a). [48] In CPAs, one of the components, the low-cytotoxic CD-based PGEAs (CPs) were prepared to complex with p53 for gene therapy of tumor. The other components, ferrocene-modified zinc tetraaminophthalocyanine (TAPc-Fc) units, served as photosensitizers.…”