NIR-triggered upconversion nanocarriers for synergistic photodynamic therapy and carbon monoxide therapy

Mesoporous silica-coated upconversion nanoparticles provide a versatile hybrid platform for combining light-responsive therapeutic functions because their porous structure offers high surface area, tunable loading capacity, and controllable molecular transport, while the upconversion core enables activation by tissue-penetrating near-infrared (NIR) light. 
In this study, we developed a mesoporous silica-coated multi-shell upconversion nanoparticle (MUmS) nanoplatform for the combined delivery of a photosensitizer (PS) and a manganese carbonyl (MnCO)-based carbon monoxide (CO) donor. The multi-shell upconversion nanoparticle was designed to enhance red upconversion luminescence under 808 nm irradiation, thereby facilitating PS activation and singlet oxygen generation. A mesoporous silica layer was subsequently introduced as a chemically stable and biocompatible reservoir that accommodates both therapeutic components and improves aqueous dispersibility and colloidal stability. Upon NIR irradiation, the MUmS platform converted low-energy excitation light into high-energy visible emission, activating the PS and generating singlet oxygen. 
In addition, the MnCO payload released CO in a controlled manner, providing a gas therapeutic effect by disrupting tumor cell metabolism. This dual-action mechanism was designed to overcome the limited efficacy of single-mode phototherapy by simultaneously inducing oxidative damage via photodynamic therapy and perturbing cellular homeostasis via CO-mediated gas therapy. The co-localization of the PS and CO donor within the mesoporous silica shell further supports coordinated therapeutic activation from a single nanocarrier. As a result, the MUmS system demonstrates the potential of mesoporous inorganic–organic hybrid nanostructures as NIR-responsive delivery platforms for multimodal cancer therapy.