Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Pharm Res. 2023 Jan;40(1):3-25. doi: 10.1007/s11095-023-03471-7. Epub 2023 Feb 3.
Endothelial cells play critical roles in circulatory homeostasis and are also the gateway to the major organs of the body. Dysfunction, injury, and gene expression profiles of these cells can cause, or are caused by, prevalent chronic diseases such as diabetes, cardiovascular disease, and cancer. Modulation of gene expression within endothelial cells could therefore be therapeutically strategic in treating longstanding disease challenges. Lipid nanoparticles (LNP) have emerged as potent, scalable, and tunable carrier systems for delivering nucleic acids, making them attractive vehicles for gene delivery to endothelial cells. Here, we discuss the functions of endothelial cells and highlight some receptors that are upregulated during health and disease. Examples and applications of DNA, mRNA, circRNA, saRNA, siRNA, shRNA, miRNA, and ASO delivery to endothelial cells and their targets are reviewed, as well as LNP composition and morphology, formulation strategies, target proteins, and biomechanical factors that modulate endothelial cell targeting. Finally, we discuss FDA-approved LNPs as well as LNPs that have been tested in clinical trials and their challenges, and provide some perspectives as to how to surmount those challenges.
内皮细胞在循环稳态中起着至关重要的作用，也是身体主要器官的门户。这些细胞的功能障碍、损伤和基因表达谱可能导致或由常见的慢性疾病引起，如糖尿病、心血管疾病和癌症。因此，内皮细胞中基因表达的调控可能在治疗长期存在的疾病挑战方面具有治疗策略意义。脂质纳米颗粒 (LNP) 已成为递送核酸的有效、可扩展和可调的载体系统，使其成为向内皮细胞递送基因的有吸引力的载体。在这里，我们讨论了内皮细胞的功能，并强调了一些在健康和疾病期间上调的受体。综述了 DNA、mRNA、circRNA、saRNA、siRNA、shRNA、miRNA 和 ASO 递送至内皮细胞及其靶标的应用和实例，以及 LNP 的组成和形态、制剂策略、靶蛋白和调节内皮细胞靶向的生物力学因素。最后，我们讨论了已获得 FDA 批准的 LNP 以及已在临床试验中测试的 LNP 及其挑战，并就如何克服这些挑战提供了一些观点。
