Near-Infrared Light-Triggered <i>In Situ</i> Construction of 3D "Fishing Net" Polymer Networks Using Upconversion Nanoparticles for Tumor Therapy.

Abstract

<i>In situ</i> construction of three-dimensional (3D) polymer networks for tumor cell capture, localization, and killing provides a different option for precision tumor therapy. Current approaches, however, face limitations due to insufficient and heterogeneous endogenous polymerization stimuli and the phototoxicity and limited tissue penetration of ultraviolet (UV)/visible light-triggered exogenous polymerization, constraining effective <i>in vivo</i> network assembly. We present a near-infrared (NIR) light-driven strategy utilizing the upconversion properties of thulium-doped core-shell nanoparticles (UCNPs) to enable precise, localized <i>in situ</i> polymerization within tumor cells. The UCNPs convert NIR (980 nm) light with better penetration depth to UV wavelengths (345 and 360 nm), activating photoinitiated radical polymerization. Hence, enhancing the emission of UCNPs in the UV region is crucial for UV-induced <i>in situ</i> polymerization. Herein, by systematically elucidating the core-shell growth process, DHU-UCNPs-1 carrying polymerized components is elaborated, and their emission intensities at 345 and 360 nm are enhanced by 113.7-fold and 84.8-fold compared to the luminescent core, respectively. The nanoplatform forms an inorganic-polymer hybridized 3D fibrous network upon <i>in situ</i> polymerization. Of note, this "fishing net" polymer network disrupts actin dynamics, impedes cell migration, and compromises mitochondrial function, collectively suppressing tumor growth and metastasis. Featuring NIR-triggered control, deep-tissue accessibility, and broad monomer compatibility, this platform provides a promising paradigm for <i>in situ</i> 3D polymer network assembly, advancing the applications of UCNPs in tumor therapy and beyond.