A multifunctional alginate-based platform (
1-Alg-2@DSS
) was developed to integrate therapeutic drug delivery with fluorescence-based safety monitoring. A bioactive microbial-derived modifier and a naphthalimide fluorophore were covalently grafted onto an alginate backbone to construct a stable carrier for Danshensu (DSS) loading. The obtained composite displayed favorable physicochemical stability, mesoporosity, and environment-sensitive fluorescence properties. In a β-glycerophosphate-induced vascular smooth muscle cell (VSMC) calcification model, DSS-loaded
1-Alg-2
exhibited good biocompatibility and effectively attenuated senescence and osteogenic phenotypic switching. Relative to free DSS, it more strongly reduced the expression of osteogenic and senescence-related markers, including Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) p21, interleukin-6 (IL-6), and restored sirtuin 1 (SIRT1) expression. In addition, the naphthalimide-functionalized alginate framework achieved highly selective fluorescence sensing of nitrofurazone (NFZ), with a Stern–Volmer quenching constant of 9.87 × 10
5
M⁻
1
and a response time of 1 min, together with excellent reversibility and anti-interference capability. These results demonstrate a versatile alginate-based platform that combines vascular protective therapy with fluorescence monitoring of harmful antibiotic residues.