All-in-one theranostic nanoplatform with controlled drug release and activated MRI tracking functions for synergistic NIR-Ⅱ hyperthermia-chemotherapy of tumors

Real-time tracking drug release behavior is fundamentally important for avoiding adverse effects or unsuccessful treatment in personalize medical treatment. However, the development of a non-invasive drug reporting platform still remains challenging. Herein the design of a novel synthetic magnetic resonance imaging (MRI) agent for drug release tracking (SMART) is reported, which integrates photothermal core and paramagnetic ion/drug loading shell with a thermal valve in a hybrid structure. Through near-infrared (NIR)-Ⅱ photothermal effect originating from inner Au-Cu₉S₅ nanohybrid core, burst release of drugs loaded in the mesoporous silica shell is achieved. The concomitant use of a phase change material not only prevents premature drug release, but also regulates heating effect, keeping local temperature below 45 ℃, enabling synergistic chemotherapy and mild hyperthermia in vitro and in vivo. Furthermore, the drug release from SMART facilitates proton accessibility to the paramagnetic ions anchored inside mesopores channels, enhancing longitudinal T₁ relaxation rate and displaying positive signal correlation to the amount of released drug, thus allowing non-invasive real-time monitoring of drug release event. The current study highlights the potential of designed MRI nanophores such as SMART for real-time and in-situ monitoring of drug delivery for precision theranostic applications.