Smart Immunomodulating Nanocomposites Enabling on-Demand Solid Tumor Treatment With Quasi-Real-Time Response Monitoring.

Recent advances in cancer immunotherapy face challenges such as limited efficacy in solid tumors, adverse effects, and prohibitive costs. This study addresses these challenges by developing a theranostic magnetic nanocomposite (mNC) system for on-demand delivery of small-molecule immunomodulating drugs (smIDs) to solid tumors. This system enables externally triggered drug release under alternating magnetic fields (AMFs) and simultaneous MRI monitoring. Functionalization with a granzyme B (GzmB)-responsive fluorescent probe allows real-time assessment of immune activation, focusing on NK cells and CTLs. In vitro and ex vivo validation demonstrated effective mobilization of innate and adaptive immune responses, resulting in approximately 60% tumor cell viability reduction correlating with GzmB activity and increased cytokine release. Validation further demonstrated the ability of the system to report tumor accumulation (via MRI) and immune cell activation (optical imaging). This platform offers precise spatio-temporal control of immunotherapy delivery combined with noninvasive imaging and immune response monitoring, representing a promising strategy for enhancing the specificity and efficacy of cancer immunotherapies.