Supramolecular Valves Functionalized Rattle-Structured UCNPs@hm-SiO2 Nanoparticles with Controlled Drug Release Triggered by Quintuple Stimuli and Dual-modality Imaging Functions: A Potential Theranostic Nanomedicine

Integrating multimodality bioimaging and multiple stimuli-responsive controlled drug release properties into one single nanosystem for therapeutic application is highly desirable, but still remains a challenge. Herein, we coated a hollow mesoporous silica shell onto upconversion nanoparticles (UCNPs), conjugated pillarene-based supramolecular valves onto surface of UCNPs@hm-SiO2 using amine-coumarin phototriggers to obtain the multifunctional nanoparticles, UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5]. Benefiting from the core-shell structured UCNPs, the UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5] can serve as the efficient contrast agents for upconversion luminescence and T1-weighted magnetic resonance imaging in vitro/in vivo. More importantly, depending on exquisitely designed supramolecular valves, UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5] can realize zero-premature release under normal physiological conditions (pH 7.4), which produces the minimal damage to normal tissue, whereas this nanosystem can respond to several disease-related s...