Fluorinated Polyethylenimine to Enable Transmucosal Delivery of Photosensitizer-Conjugated Catalase for Photodynamic Therapy of Orthotopic Bladder Tumors Post-intravesical Instillation
Guangzhi Li,1 Simin Yuan,1 Dashi Deng,1 Tong Ou,1 Yuqing Li,1 Rui Sun,1 Qifang Lei,1 Xisheng Wang,1 Wanwan Shen,2 Yiyun Cheng,*2 Zhuang Liu,*3 and Song Wu*1
1Institute of Urology The Affiliated Luohu Hospital of Shenzhen University Shenzhen University Shenzhen 518000, China
2Shanghai Key Laboratory of Regulatory Biology School of Life Sciences East China Normal University Shanghai 200241, China
3Institute of Functional Nano & Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices Soochow University Suzhou 215123, China
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 CATCe6/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.