Near‐Infrared Light Triggered Intelligent Nanoplatform for Synergistic Chemo‐Photodynamic Therapy of Tumor

Abstract Chemo‐photodynamic therapy nanodelivery systems provide a potential strategy to enhance anticancer effect. However, the treatment efficiency of stimuli‐responsive nanotheranostics remains a challenge owing to off‐target properties, poor tissue penetration, and slow drugs release. Herein, di‐selenide‐bridged mesoporous silica (Se‐Se‐mSiO₂) is introduced into a near‐infrared (NIR) light triggered and tumor microenvironment (TME)‐activated intelligent nanoplatform (UCNPs@mSiO₂‐Ce6@Se‐Se‐mSiO₂(DOX)@HA (UCSSDH)) realizing burst drug release on demand. Typically, the UCSSDH actively targets cancer cells and accumulates in tumor site through hyaluronic acid (HA). Then, under the irradiation of 980 nm NIR light, the upconverted 650 nm emission light activates photosensitizer Ce6 to produce the singlet oxygen (¹O₂) for photodynamic therapy (PDT). More importantly, ¹O₂ further cleaves di‐selenide bonds which are sensitive to reactive oxygen species (ROS), driving the rapid degradation of Se‐Se‐mSiO₂ accompanied by the burst release of doxorubicin (DOX). Consequently, UCSSDH achieves efficient chemo‐photodynamic therapy of tumors. Last but not least, the upconversion nanoparticles (UCNPs) perform upconversion luminescence (UCL) imaging to monitor the drugs delivery. Collectively, an intelligent drug delivery system integrating therapeutic, monitoring, and targeting is exploited for NIR light‐triggered synergistic tumor therapy. This study broadens fresh vision into the development of controlled drug release and provides a momentous thought for potential clinical cancer therapy.