Phosphatase and tensin homolog (PTEN) antagonizes muscle growth and repair, and inhibition of PTEN has been shown to improve the pathophysiology and dystrophic muscle function in a mouse model of Duchenne muscular dystrophy (DMD). However, conventional pharmacological delivery of PTEN inhibitors carries a high risk of off-target side effects in other non-muscle organs due to broad targeting spectrums. Here we report a muscle-targeted nanoparticulate platform for cell-specific delivery of a PTEN inhibitor. Poly(lactide-co-glycolide)-b-poly(ethylene glycol) nanoparticles (NPs) are functionalized with a muscle-homing peptide M12 to promote the selective uptake by muscle cells/tissue in vitro and in vivo. Moreover, the NPs are formulated to slowly release the PTEN inhibitor, preventing cytotoxicity associated with direct exposure to the drug and facilitating sustained inhibition of PTEN. This advanced delivery approach taking advantages of polymeric nanomaterials and muscle-homing peptides opens a new avenue for the development of long-term therapeutic strategies in DMD treatment.

磷酸酶和张力蛋白同系物 (PTEN) 拮抗肌肉生长和修复，抑制 PTEN 已被证明可以改善杜氏肌营养不良症 (DMD) 小鼠模型的病理生理学和营养不良性肌肉功能。然而，由于广泛的靶向谱，PTEN 抑制剂的常规药理学递送在其他非肌肉器官中具有很高的脱靶副作用风险。在这里，我们报告了一种用于细胞特异性递送 PTEN 抑制剂的肌肉靶向纳米颗粒平台。聚（丙交酯-共-乙交酯） -b-聚（乙二醇）纳米颗粒 (NP) 被肌肉归巢肽 M12 功能化，以促进肌肉细胞/组织在体外和体内的选择性摄取。此外，NPs 被配制为缓慢释放 PTEN 抑制剂，防止与直接接触药物相关的细胞毒性并促进 PTEN 的持续抑制。这种利用聚合物纳米材料和肌肉归巢肽的先进递送方法为 DMD 治疗的长期治疗策略的发展开辟了一条新途径。