A Programmable Hybrid DNA Nanogel for Enhanced Photodynamic Therapy of Hypoxic Glioma
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RESEARCH ARTICLE
A Programmable Hybrid DNA Nanogel for Enhanced Photodynamic Therapy of Hypoxic Glioma Ye Yuan1 · Huiting Zhao1 · Yunhua Guo1 · Jianpu Tang1 · Chunxia Liu1 · Linghui Li1 · Chi Yao1 · Dayong Yang1 Received: 26 May 2020 / Revised: 10 June 2020 / Accepted: 16 June 2020 © Tianjin University and Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Photodynamic therapy (PDT) is a promising cancer therapy due to the evident advantages of a rapid curative effect, minimal or non-invasiveness, and circumvention of drug resistance. However, the hydrophobicity of photosensitizers and the hypoxic tumor microenvironment in solid tumors reduce the therapeutic effect of PDT immensely. Herein, we construct a programmable hybrid mesoporous silica nanoparticle/DNA nanogel (H-DNA nanogel) for enhanced PDT. The H-DNA nanogel is constituted with a virus-like mesoporous silica nanoparticle (VMSN) as the core to provide an appropriate nano-interface and a self-assembly programmable DNA hydrogel layer based on rolling circle amplification (RCA) as the shell. Two kinds of G-quadruplex structures inserted with a hemin and zinc phthalocyanine (ZnPc) photosensitizer are introduced into the H-DNA nanogel by base pairing. The two modules of G-quadruplex structure work as an oxygen supplement in the hypoxic tumor microenvironment and increase the yield of singlet oxygen, respectively. Our hybrid DNA nanogel system provides a modular platform for efficient cancer PDT and has great potential in the broader biomedical field. Graphic Abstract
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H-DNA nanogel O2 Cellular uptake
Laser 1O
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Keywords DNA nanogel · Rolling circle amplification · Mesoporous silica nanoparticle · Photodynamic therapy
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12209-020-00260-w) contains supplementary material, which is available to authorized users. Ye Yuan and Huiting Zhao contributed equally to this work. * Chi Yao [email protected] Extended author information available on the last page of the article
Introduction Photodynamic therapy (PDT) takes advantage of reactive oxygen species (ROS), especially singlet oxygen (1O2), to cause cancer cell apoptosis by oxidative damage, and ROS are usually generated from tissue oxygen by photosensitizers under laser irradiation [1–4]. Due to its merits, which include a rapid curative effect, minimal or non-invasiveness,
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and circumvention of drug resistance, PDT is a prospective therapeutic route with safety and efficiency in the field of cancer therapy [5–7]. However, as hydrophobic organic molecules, photosensitizers always have poor solubility in the blood, causing low drug delivery efficiency and limited yield of 1O2, which impacts the efficacy of PDT [8, 9]. In addition, the hypoxic tumor microenvironment restricts the supply of O2, which in turn weakens the therapeutic effect of PDT [10–12]. Thus, it is necessary to exploit a multifunctional delivery vehicle for both loading the photosensitizer and over
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