A smart INH-loaded nanosensor for theranostic intervention in Mtb-infected macrophages

In this study, we developed a smart isoniazid (INH)-loaded nanosensor (1-HA-DPTMS@CP1@INH) that integrates dual theranostic functions, therapeutic drug delivery, and real-time fluorescence monitoring, for the targeted treatment of osteoarticular tuberculosis (OATB). The nanoplatform, constructed from a cobalt-based coordination polymer (CP1), hyaluronic acid (HA), and fluorinated silane, exhibited excellent biocompatibility, active CD44-mediated targeting, and highly selective INH detection via fluorescence quenching (KSV = 550.82 M⁻ 1 ). Compared with conventional single-function nanosystems, this hybrid design enables simultaneous sensing and controlled release of INH, featuring efficient drug loading, pH-responsive release, and stable fluorescence performance even under physiological interference. In vitro studies on Mycobacterium tuberculosis (Mtb)-infected RAW 264.7 macrophages confirmed that 1-HA-DPTMS@CP1@INH effectively inhibited inflammatory cytokine secretion and downregulated bone-destructive enzymes (CatK and MMP9), thereby alleviating the inflammatory microenvironment. Collectively, this work presents a clinically translatable nanoplatform that offers a promising strategy for simultaneous diagnosis and therapy of OATB.