期刊
ADVANCED FUNCTIONAL MATERIALS
卷 29, 期 40, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201901932
关键词
bladder cancer; bladder instillation-based PDT; cell-penetrating and transmucosal delivery; fluorinated polymer; tumor hypoxia
类别
资金
- Shenzhen Basic Research (Layout of Disciplines) [JCYJ20160429093033251, JCYJ20170412155305340]
- National Key Basic Research Program of China [2015CB755501]
- National Research Programs from the Ministry of Science and Technology (MOST) of China [2016YFA0201200, 2017YFA0105900]
- National Natural Science Foundation of China [51525203, 21725402, 61731018]
- China Postdoctoral Science Foundation [2018M631795, 2018M631794]
- Shenzhen Basic Research Project [JCYJ20170818110648802]
- Guangdong Medical Science and Technology Research Fund [B2019016]
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
- Fund for Shenzhen Public Platform for Clinical Genetic Services [2015170924]
Photodynamic therapy (PDT) by insertion of an optical fiber into the bladder cavity has been applied in the clinic for noninvasive treatment of bladder tumors. To avoid systemic phototoxicity, bladder intravesical instillation of a photosensitizer may be an ideal approach for PDT treatment of bladder cancer, in comparison to conventional intravenous injection. However, the instillation-based PDT for bladder cancer treatment remains to be less effective due to the poor urothelial uptake of photosensitizer, as well as the tumor hypoxia-associated PDT resistance. Herein, it is uncovered that fluorinated polyethylenimine (F-PEI) achieved by mixing with Chorin-e6-conjugated catalase (CAT-Ce6) is able to form self-assembled CAT-Ce6/F-PEI nanoparticles, which show greatly improved cross-membrane, transmucosal, and intratumoral penetration capacities compared with CAT-Ce6 alone or nonfluorinated CAT-Ce6/PEI nanoparticles. Owing to the decomposition of tumor endogenous H2O2 by CAT-Ce6/F-PEI nanoparticles penetrating into bladder tumors, the tumor hypoxia would be effectively relieved to further favor PDT. Therefore, bladder intravesical instillation with CAT-Ce6/F-PEI nanoparticles could offer remarkably improved photodynamic therapeutic effect to destruct orthotopic bladder tumors with reduced systemic toxicity compared to hematoporphyrin, the first-line photosensitizer used for bladder cancer PDT in clinic. This work presents a unique photosensitizer nanomedicine formulation, promising for clinical translation in instillation-based PDT to treat bladder tumors.
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