A fluorescence-responsive nanoplatform for Fe³⁺ detection and baicalein delivery toward cardiomyocyte apoptosis modulation in heart failure

Heart failure (HF), a highly disabling and therapeutically challenging clinical syndrome, is primarily characterized by sustained cardiomyocyte apoptosis and an imbalanced inflammatory microenvironment. To overcome the limitations of conventional therapies and enhance the anti-apoptotic and anti-inflammatory efficacy of the natural flavonoid baicalin, we developed a multifunctional nanoparticle-based delivery platform incorporating a hybrid structure of natural polysaccharides and metal–polymer frameworks. Specifically, the fluorescent small molecule (compound 1) was grafted onto oxidized Astragalus polysaccharide (OAPS), followed by the incorporation of polymeric silica (DPTMS) to improve structural stability. This composite was further employed to encapsulate a copper-based coordination polymer (CP1), forming the nanocomposite 1-OAPS-DPTMS@CP1@Baicalein, which enables efficient baicalin loading and controlled release. This system exhibits excellent water dispersibility, high drug-loading capacity, and Fe³⁺-induced fluorescence quenching behavior, offering potential for real-time tracking and diagnostic applications. In vitro functional assays demonstrated that 1-OAPS-DPTMS@CP1@Baicalein significantly improved cell viability in TNF-α/IL-1β-stimulated cardiomyocytes, downregulated pro-apoptotic markers (e.g., Bax and caspase-3), restored anti-apoptotic Bcl-2 levels, and markedly reduced the secretion of inflammatory cytokines IL-6 and TNF-α, highlighting its promising dual-function therapeutic potential in anti-inflammatory and anti-apoptotic treatment of HF.