Engineering a bi-functional nanoplatform containing FH peptide for preferential cardiac delivery to counteract doxorubicin-induced cardiotoxicity

BACKGROUND: DOX, an anthracycline antibiotic, is extensively utilized in the treatment of various solid tumors and hematological malignancies but is constrained by its cumulative cardiotoxicity. PDA has emerged as a promising drug delivery platform owing to its superior biocompatibility, pH-responsive drug release capability, and multifunctional surface properties.The FH peptide, which specifically targets Tenascin-C overexpressed in DOX-injured myocardium, offers a promising strategy to enhance cardiac-specific drug accumulation. METHODS: In vitro experiments were performed using primary neonatal mouse cardiomyocytes. Cardioprotective efficacy was evaluated in an acute DOX-induced myocardial injury mouse model, and antitumor activity was assessed in a 4T1 tumor-bearing mouse model. RESULTS: Our comprehensive analysis, including spectroscopic methods and physicochemical characterization, confirmed the successful integration of Dex and FH onto the PDA platform. Both in vitro and in vivo studies demonstrated that PDA-Dex/FH effectively treats DOX-induced cardiotoxicity, with FH incorporation enhancing cardiac targeting while preserving DOX's antitumor efficacy. CONCLUSIONS: we demonstrated that, under the experimental conditions of this study, PDA-Dex/FH not only markedly mitigates myocardial injury with enhanced cardiac accumulation but also retains the chemotherapeutic efficacy of doxorubicin, thereby.