Su Teng, Huang Ke, Ma Hong, Liang Hongxia, Dinh Phuong-Uyen, Chen Justin, Shen Deliang, Allen Tyler A, Qiao Li, Li Zhenhua, Hu Shiqi, Cores Jhon, Frame Brianna N, Young Ashlyn T, Yin Qi, Liu Jiandong, Qian Li, Caranasos Thomas G, Brudno Yevgeny, Ligler Frances S, Cheng Ke
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North, Carolina State University, Raleigh, NC 27695, USA.
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Adv Funct Mater. 2019 Jan 24;29(4). doi: 10.1002/adfm.201803567. Epub 2018 Nov 13.
Cardiovascular disease is the leading cause of mortality worldwide. While reperfusion therapy is vital for patient survival post-heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post-ischemic recovery. A platelet-inspired nanocell (PINC) that incorporates both prostaglandin E2 (PGE)-modified platelet membrane and cardiac stromal cell-secreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct-homing ability of platelet membrane and the overexpression of PGE receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be achieved by PINC, which combines the paracrine mechanism of cell therapy with the PGE/EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury.
心血管疾病是全球范围内的主要死因。虽然再灌注疗法对心脏病发作后的患者生存至关重要，但它也会导致进一步的组织损伤，在临床实践中称为心肌缺血/再灌注（I/R）损伤。探索减轻I/R损伤的方法对于改善缺血后恢复具有临床意义。本文介绍了一种受血小板启发的纳米细胞（PINC），它结合了前列腺素E2（PGE）修饰的血小板膜和心脏基质细胞分泌的因子，用于在I/R损伤后靶向心脏。通过利用血小板膜的天然梗死归巢能力以及I/R损伤后病理性心脏微环境中PGE受体（EPs）的过表达，PINC可以实现治疗性药物向受损心脏的靶向递送。此外，PINC可以实现协同治疗效果，它将细胞治疗的旁分泌机制与参与多种组织修复和再生的PGE/EP受体信号传导相结合。在心肌I/R损伤的小鼠模型中，静脉注射PINC可增强心脏功能并减轻心脏重塑，同时伴有循环心肌细胞增加、内源性干/祖细胞激活和血管生成促进。这种方法代表了一种治疗I/R损伤的有前景的治疗递送平台。
