Mineralized manganese dioxide channel as the stent coating for in situ precise tumor navigation
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Mineralized manganese dioxide channel as the stent coating for in situ precise tumor navigation Junyuan Xiao1,2,§, Yiran Zhang1,2,§, Tonglei Fang1, Tianwen Yuan4, Qinghua Tian1, Jingjing Liu1, Yingsheng Cheng1 (), Yueqi Zhu1 (), Liang Cheng3 (), and Wenguo Cui2 () 1
Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yishan Road, Shanghai 200233, China Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 3 Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China 4 Depatment of Interventional Oncology, Dahua Hospital, Xuhui District, Shanghai 200237, China § Junyuan Xiao and Yiran Zhang contributed equally to this work. 2
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 Received: 25 July 2020 / Revised: 6 September 2020 / Accepted: 12 September 2020
ABSTRACT Drug-eluting stent (DES) is a promising strategy for esophageal cancer. However, full-covered drug-loaded stents cause damage to non-tumor tissue in the esophagus, and the development controlled-release system to prevent non-tumor tissue injure is currently a major challenge. Here, in situ mineralized manganese dioxide coating on Ce6 embedded electrospun fibers covered stent was developed for effective tumor therapy via intraluminal photodynamic therapy (PDT), which could reduce phototoxicity to normal esophageal tissue. Oxidation of manganese ions, which was previously swelled between fibers, was used to accomplish mineralization. After implantation, the manganese dioxide coating in situ reacts with tumor endogenous H+ and H2O2, which, on the one hand, could effectively alleviate the hypoxic microenvironment which leads to resistance to PDT, and on the other hand, could expose the Ce6-fibers below the coating for intraluminal PDT. In addition, due to the slow degradation of the coating, this stent could own sustained photodynamic performance for up to one month. Notably, the PDT efficiency of the stent was investigated on orthotopic rabbit esophageal cancer models. Overall, this work suggests that in situ mineralized manganese dioxide coated electrospun fibers covered stent may provide a new strategy for advanced esophageal cancer patients as a functional drug delivery platform.
KEYWORDS electrospinning, manganese dioxide, tumor hypoxia, photodynamic therapy, stent
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Introduction
Drug-eluting stents (DESs) is currently the first choice for the treatment of esophageal stenosis [1–7]. On the one hand, the stenosis could be immediately dilated. On the other hand, drugs released from the stent could inhabit tissue proliferation [8]. Besides, DESs have the advantage of increasing local drug accumulation and reducing system side effects compared to bare stent plus intravenous drug therapy
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