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      Fluorinated Chitosan To Enhance Transmucosal Delivery of Sonosensitizer-Conjugated Catalase for Sonodynamic Bladder Cancer Treatment Post-intravesical Instillation

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          Abstract

          <p class="first" id="d34545566e208">Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with meso-tetra(4-carboxyphenyl)porphine-conjugated catalase (CAT-TCPP). The formed CAT-TCPP/FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O2 generation from tumor endogenous H2O2 to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity. </p>

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          Author and article information

          Contributors
          Journal
          ACS Nano
          ACS Nano
          American Chemical Society (ACS)
          1936-0851
          1936-086X
          January 24 2020
          February 25 2020
          February 03 2020
          February 25 2020
          : 14
          : 2
          : 1586-1599
          Affiliations
          [1 ]Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
          [2 ]Institute of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen 518000, China
          [3 ]Department of Nephrology, The Second Hospital and Center for Renal Diseases, Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China
          [4 ]School of Material Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
          [5 ]Department of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China
          [6 ]Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
          Article
          10.1021/acsnano.9b06689
          32011860
          6e8eb47f-7cc1-4887-b05b-d7815266609b
          © 2020
          Product
          Self URI (article page): https://pubs.acs.org/doi/10.1021/acsnano.9b06689

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