Exosomes are promising therapeutics for tissue repair and regeneration to induce and guide appropriate immune responses in dystrophic pathologies. However, manipulating exosomes to control their biodistribution and targeting them in vivo to achieve adequate therapeutic benefits still poses a major challenge. Here we overcome this limitation by developing an externally controlled delivery system for primed annexin A1 myo-exosomes (Exo^myo). Effective nanocarriers are realized by immobilizing the Exo^myo onto ferromagnetic nanotubes to achieve controlled delivery and localization of Exo^myo to skeletal muscles by systemic injection using an external magnetic field. Quantitative muscle-level analyses revealed that macrophages dominate the uptake of Exo^myo from these ferromagnetic nanotubes in vivo to synergistically promote beneficial muscle responses in a murine animal model of Duchenne muscular dystrophy. Our findings provide insights into the development of exosome-based therapies for muscle diseases and, in general, highlight the formulation of effective functional nanocarriers aimed at optimizing exosome biodistribution.

外泌体是有前途的组织修复和再生疗法，可在营养不良病理中诱导和指导适当的免疫反应。然而，操纵外泌体以控制其生物分布并在体内靶向它们以实现足够的治疗效果仍然是一个重大挑战。在这里，我们通过开发一种用于引发的膜联蛋白 A1 肌外泌体 （Exo^myo） 的外部控制递送系统来克服这一限制。通过将 Exo^myo 固定在铁磁纳米管上，通过使用外部磁场进行全身注射，实现 Exo^myo 向骨骼肌的受控递送和定位，从而实现有效的纳米载体。定量肌肉水平分析显示，巨噬细胞在体内从这些铁磁纳米管中摄取外显^肌，以协同促进杜氏肌营养不良症小鼠动物模型中的有益肌肉反应。我们的研究结果为基于外泌体的肌肉疾病疗法的开发提供了见解，并且总体上强调了旨在优化外泌体生物分布的有效功能性纳米载体的配方。