期刊
ACTA BIOMATERIALIA
卷 129, 期 -, 页码 269-279出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2021.05.029
关键词
Type I sonodynamic therapy; Ultrasound irradiation; Reactive oxygen species; Hypoxia; Pancreatic cancer
资金
- National Key R&D Program of China [2018YFC0115900]
- National Natural Science Foundation of China [82030048, 81901871, 82001818]
- Key Research and Development Program of Zhejiang Province [2019C03077]
- Natural Science Foundation of Zhejiang Province [LQ19H180004, LQ20H180009, LQ21H180007]
- China Postdoctoral Science Foundation [2020T130594]
In this study, a tablet-like TiO2/C nanocomposite with a metal-organic-framework (MOF)-derived carbon structure was designed, showing great stability under repeated ultrasound irradiation, hypoxia-tolerant ability, and good biocompatibility. The TiO2/C nanocomposite could efficiently generate reactive oxygen species in an oxygen-independent manner, making it a promising tool for treating hypoxic solid pancreatic tumors with repeated type I sonodynamic therapy.
Sonodynamic therapy (SDT) represents a viable approach to overcoming the limited ability of photodynamic therapy to penetrate biological barriers. However, pancreatic tumors contain a hypoxic microenvironment that limits the efficacy of oxygen-dependent type II SDT, complicating efforts to develop reliable, stable, and hypoxia-tolerant sonosensitizer. Herein, a tablet-like TiO2/C nanocomposite with a metalorganic-framework (MOF)-derived carbon structure was designed and found to be hypoxia-tolerant and stable in response to repeated ultrasound irradiation, enabling the TiO2/C-mediated generation of large quantities of reactive oxygen species (ROS) and thereby achieving efficacious type I SDT. Importantly, this nanocomposite continued to generate ROS in response to repeated ultrasound irradiation, and was able to induce tumor cell apoptosis via SDT-induced DNA damage in vitro and in vivo. This TiO2/C nanocomposite also exhibited good biocompatibility and did not induce any apparent toxicity in vitro and in vivo. Together, these data highlight TiO2/C as a valuable nanocomposite capable of facilitating repeated type I SDT, making it a promising tool for the treatment of hypoxic solid pancreatic tumors. Statement of significance In this research, a tablet-like TiO2/C nanocomposite with a metal-organic-framework (MOF)-derived carbon structure was designed, which exhibited great stability upon repeated ultrasound irradiation, hypoxic-tolerant ability and good biocompatibility. After ultrasound irradiation, TiO2/C could efficiently generate reactive oxygen species in an oxygen-independent manner, which overcame the limitation of pure TiO2 nanoparticles. Therefore, it was applied to repeated type I sonodynamic therapy of hypoxic pancreatic tumor. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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