Fluorinated Chitosan Mediated Synthesis of Copper Selenide Nanoparticles with Enhanced Penetration for Second Near‐Infrared Photothermal Therapy of Bladder Cancer

Abstract The emergence of near‐infrared‐II (NIR‐II) light activated photomedicines has extended the penetration depth for noninvasive theranostics, especially for photothermal nanomedicines. Intravesical instillation therapy of bladder cancer (BCa) is restricted greatly due to the short residence time and the low penetration ability of therapeutic agents in clinic. Therefore, improving the mucoadhesiveness and penetration of therapeutic agents are crucial factors in treatment of BCa. The development of NIR‐II light triggered photothermal transduction agents for enhanced penetration and photothermal ablation of BCa post‐intravesical instillation has not yet been investigated. Herein, Cu 2‐ x Se biocompatible particles are prepared through a fluorinated chitosan (FCS)‐mediated one‐pot aqueous approach, which possesses enhanced penetrating ability and high photothermal conversion capability for effective NIR‐II photothermal therapy (PTT). Owing to the outstanding transmucosal ability of FCS, FCS capped Cu 2‐ x Se nanoparticles exhibit much better transmucosal and penetration performance than their non‐fluorinated counterparts to significantly improve the therapeutic efficacy of NIR‐II PTT to ablate orthotopic bladder tumors. This study presents a promising phototherapy agent based on Cu 2‐ x Se modified with FCS for efficient NIR‐II PTT for BCa treatment post‐intravesical instillation.