G-Quadruplex-Based Nanoscale Coordination Polymers to Modulate Tumor Hypoxia and Achieve Nuclear-Targeted Drug Delivery for Enhanced Photodynamic Therapy
Top Cited Papers
- 1 November 2018
- journal article
- research article
- Published by American Chemical Society (ACS) in Nano Letters
- Vol. 18 (11), 6867-6875
- https://doi.org/10.1021/acs.nanolett.8b02732
Abstract
Photodynamic therapy (PDT) is a light triggered therapy used to kill cancer cells by producing reactive oxygen species (ROS). Herein, a new kind of DNA nanostructure based on the coordination between calcium ions (Ca2+) and AS1411 DNA G quadruplexes to form nanoscale coordination polymers (NCPs) is developed via a simple method. Both chlorine e6 (Ce6), a photosensitizer, and hemin, an iron-containing porphyrin, can be inserted into the G-quadruplex structure in the obtained NCPs. With further polyethylene glycol (PEG) modification, we obtain Ca-AS1411/Ce6/hemin@pHis-PEG (CACH-PEG) NCP nanostructure that enables the intranuclear transport of photosensitizer Ce6 to generate ROS inside cell nuclei that are the most vulnerable to ROS. Meanwhile, the inhibition of antiapoptotic protein B-cell lymphoma 2 (Bcl-2) expression by AS1411 allows for greatly improved PDT-induced cell apoptosis. Furthermore, the catalase-mimicking DNAzyme function of G-quadruplexes and hemin in those NCPs could decompose tumor endogenous H2O2 to in situ generate oxygen so as to further enhance PDT by overcoming the hypoxia-associated resistance. This work develops a simple yet general method with which to fabricate DNA-based NCPs and presents an interesting concept of a nanoscale drug-delivery system that could achieve the intranuclear delivery of photosensitizers, the down-regulation of antiapoptotic proteins, and the modulation of the unfavorable tumor microenvironment simultaneously for improved cancer therapy.Funding Information
- Universidade de Macau (MYRG2016-00130-ICMS-QRCM, MYRG2017-00182-ICMS)
- Ministry of Science and Technology of the People's Republic of China (2016YFA0201200)
- Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia (096/2015/A3)
- National Natural Science Foundation of China (51525203, 81403120)
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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