X‐ray Radiation‐Controlled NO‐Release for On‐Demand Depth‐Independent Hypoxic Radiosensitization

Abstract Multifunctional stimuli‐responsive nanotheranostic systems are highly desirable for realizing simultaneous biomedical imaging and on‐demand therapy with minimized adverse effects. Herein, we present the construction of an intelligent X‐ray‐controlled NO‐releasing upconversion nanotheranostic system (termed as PEG‐USMSs‐SNO) by engineering UCNPs with S‐nitrosothiol (R‐SNO)‐grafted mesoporous silica. The PEG‐USMSs‐SNO is designed to respond sensitively to X‐ray radiation for breaking down the SN bond of SNO to release NO, which leads to X‐ray dose‐controlled NO release for on‐demand hypoxic radiosensitization besides upconversion luminescent imaging through UCNPs in vitro and in vivo. Thanks to the high live‐body permeability of X‐ray, our developed PEG‐USMSs‐SNO may provide a new technique for achieving depth‐independent controlled NO release and positioned radiotherapy enhancement against deep‐seated solid tumors.