Author:
Zhou Daijun,Du Min,Luo Han,Ran Fengwei,Zhao Xiang,Dong Yan,Zhang Tao,Hao Jie,Li Dong,Li Jianjun
Abstract
AbstractRadiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.
Funder
the Medical and Industrial Combination Cultivation Program of Southwest Jiaotong University
the Program of General Hospital of Western Theater Command of PLA
国家自然科学基金委员会
the Military Program of Army Medical University
The General Program of Chongqing Natural Science Foundation
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
Cited by
16 articles.
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