Macrophage membrane camouflaged biomimetic nanomedicine for normalizing electrical dysfunction and inflammation pathology in atrial fibrillation.

Atrial fibrillation (AF), the common sustained tachyarrhythmia in clinical practice, is characterized by a pathophysiology with electrical dysfunction and inflammation. To overcome the challenges of low bioavailability, short pharmacokinetic half-life and severe adverse effects of Amiodarone (AMD), a macrophage membrane-biomimetic nanotherapeutic platform (MM@AMDNPs) was developed for enhancing the target delivery and sustained AMD release. Given the inherited biological activity from macrophage, MM@AMDNPs is able to specifically localize to AF-associated inflammatory lesion, enabling interference with electrical remodeling while mitigating AMD-related pulmonary toxicity, i.e., compared with the uncoated nanoparticles, MM@AMDNPs prolongs 2.03-fold blood circulation half-life, enhances 1.7-fold target accumulation at AF lesions, reduces macrophage phagocytosis by 65.5%, alleviates AF inducibility from 100% to 20%, shortens AF duration from 132.8 ± 26.2 s to 0.8 ± 1.8 s at 4 h post-administration, normalizes the inflammatory marker iNOS and fibrotic marker TGF-β1 in lung tissues without any significant pulmonary histopathological injury. Hence, MM@AMDNPs represents a promising therapeutic platform for safe and effective antiarrhythmic therapy.