A dual chemical-photothermal drug delivery platform inhibits LPS-induced oxidative damage by suppressing the p38 MAPK pathway in cardiomyocytes

Heart failure (HF) is a complex clinical syndrome marked by impaired cardiac function, often driven by cardiomyocyte apoptosis. The latter is induced by myocardial infarction, atherosclerosis, or ischemia-reperfusion injury, with oxidative stress playing a central role in progression. In this study, a therapeutic molecule (compound I) targeting HF was synthesized and loaded into a zwitterionic amphiphilic polymer nanocarrier system (PSBMA-CP1@I), constructed via coordination between compound I and CP1. The structural and optical properties of PSBMA-CP1@I were systematically characterized. Fluorescence spectroscopy revealed that the introduction of compound I led to significant emission quenching of the PSBMA-CP1 scaffold under 365 nm excitation (from ∼432 nm), indicating successful drug loading. Fluorescence titration experiments conducted in the 0–2400 pM range showed a concentration-dependent response with a Stern–Volmer quenching constant (KSV) of 1.63 × 10⁶ M⁻1 and good linearity in the low concentration region (0–750 pM, R2 = 0.9930), demonstrating high detection sensitivity. pH-responsive release tests indicated enhanced release of compound I under acidic conditions (pH 5.0), with a cumulative release of up to 75% within 60 minutes, compared to a much slower release at pH 7.4. Moreover, in vitro studies in lipopolysaccharide (LPS)-stimulated H9C2 cells showed that PSBMA-CP1@I effectively attenuates oxidative damage and modulates p38-MAPK signaling, supporting its application in anti-inflammatory and cardioprotective therapies.