Silicon-polysaccharide fluorescent nanocomposite for everolimus delivery and theranostic application in clear cell renal cell carcinoma.

Everolimus showed therapeutic promise in treating clear cell renal cell carcinoma (ccRCC), yet its efficacy was limited by poor bioavailability and weak tumor targeting. In this study, we developed a multifunctional Co(II)-based MOF (CP1) using H4L and bpp ligands, forming a 3D (4,8)-connected framework. To enhance stability and functionality, CP1 was coated with sodium alginate (SA) and APTMS, and further modified with a fluorescent benzopyranone derivative (compound 1) via Ullmann-type coupling, yielding 1-SA-APTMS@CP1. The final nanocarrier, 1-SA-APTMS@CP1@EVE, exhibited a high surface area (98.3 m2/g), mesoporosity (2-6 nm), and strong structural integrity. It enabled dual-channel fluorescence detection of GSH and NAD(P)H, with detection limits of 233 pM and 65 nM, respectively. In vitro, the system effectively inhibited ccRCC cell proliferation and downregulated TNFRSF18, a key immunomodulatory gene. This study provides a redox-responsive, fluorescence-trackable delivery platform for everolimus, offering potential for targeted and immune-synergistic therapy in ccRCC.