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

Abstract

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.

• Authors: Guangzhi Li, Shupeng Wang, Dashi Deng, Zhisheng Xiao, Ziliang Dong, Zhiping Wang, Qifang Lei, Shan Gao, Guixiao Huang, Enpu Zhang, Guohua Zeng, Zhong Wen, Song Wu, Zhuang Liu
• Journal: ACS nano (ACS Nano) Vol. 14 Issue 2 Pg. 1586-1599 (02 25 2020) ISSN: 1936-086X [Electronic] United States
• PMID: 32011860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Photosensitizing Agents
• Porphyrins
• tetracarboxyphenylporphine
• Chitosan
• Catalase

Topics

• Administration, Intravesical
• Animals
• Catalase (chemistry, metabolism)
• Cell Line, Tumor
• Chitosan (administration & dosage, chemistry, metabolism)
• Drug Delivery Systems
• Halogenation
• Mice
• Molecular Structure
• Nanoparticles (administration & dosage, chemistry, metabolism)
• Particle Size
• Photosensitizing Agents (chemistry, metabolism, therapeutic use)
• Porphyrins (chemistry, metabolism, therapeutic use)
• Surface Properties
• Ultrasonic Therapy
• Urinary Bladder Neoplasms (drug therapy, metabolism)