Fluorescent Nanocomposite Materials with Synergistic Effects for Enhanced Fenelidone Delivery in Diabetic Nephropathy Treatment.

In this study, we designed and synthesized a novel thio-purine analog, compound 1, which exhibits significant fluorescence properties due to its extended conjugated system, heteroatom incorporation (O, S, N), and rigid three-dimensional molecular framework, enabling its use as a fluorescence probe for real-time drug tracking and release monitoring. To enhance the solubility, biocompatibility, and therapeutic efficacy of compound 1, we synthesized a copper(II)-based coordination polymer (CP1) via hydrothermal methods, featuring a three-dimensional framework formed by 1,4-ttb and auxiliary ligand 4,4'-bpdc, as confirmed by comprehensive characterization techniques. Leveraging the synergistic therapeutic effects of compound 1 and fenelidone, we developed a composite drug delivery system, mPEG-PSU@CP1@1@fenelidone, which combines an amphiphilic mPEG-PSU shell with a CP1 core co-encapsulating both drugs. Notably, the fluorescence properties of compound 1 allow for real-time monitoring of drug release, as its fluorescence is quenched when encapsulated in CP1 and restored upon release. This system optimizes controlled drug release while enhancing the synergistic effects of compound 1 and fenelidone in reducing inflammation and renal fibrosis, as demonstrated in diabetic nephropathy (DN) model mice. Overall, the composite system integrates real-time fluorescence monitoring with improved therapeutic efficacy, offering a promising strategy for diabetic nephropathy treatment.