Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine Karolinska Institutet, Stockholm, Sweden.
Cancer Research Laboratory, Shandong University-Karolinska Institutet collaborative Laboratory, School of Basic Medical Science, Shandong University, Jinan, Shandong, PR China.
J Extracell Vesicles. 2022 Jul;11(7):e12248. doi: 10.1002/jev2.12248.
Extracellular vesicles (EVs) have shown promise as potential therapeutics for the treatment of various diseases. However, their rapid clearance after administration could be a limitation in certain therapeutic settings. To solve this, an engineering strategy is employed to decorate albumin onto the surface of the EVs through surface display of albumin binding domains (ABDs). ABDs were either included in the extracellular loops of select EV-enriched tetraspanins (CD63, CD9 and CD81) or directly fused to the extracellular terminal of single transmembrane EV-sorting domains, such as Lamp2B. These engineered EVs exert robust binding capacity to human serum albumins (HSA) in vitro and mouse serum albumins (MSA) after injection in mice. By binding to MSA, circulating time of EVs dramatically increases after different routes of injection in different strains of mice. Moreover, these engineered EVs show considerable lymph node (LN) and solid tumour accumulation, which can be utilized when using EVs for immunomodulation, cancer- and/or immunotherapy. The increased circulation time of EVs may also be important when combined with tissue-specific targeting ligands and could provide significant benefit for their therapeutic use in a variety of disease indications.
细胞外囊泡 (EVs) 作为治疗各种疾病的潜在治疗方法显示出了希望。然而,它们在给药后迅速清除可能是某些治疗环境中的限制。为了解决这个问题,采用工程策略通过表面展示白蛋白结合域 (ABDs) 将白蛋白修饰到 EV 的表面上。ABDs 要么包含在选定的 EV 富集四跨膜蛋白 (CD63、CD9 和 CD81) 的细胞外环中,要么直接融合到单跨膜 EV 分选结构域的细胞外末端,如 Lamp2B。这些工程化的 EV 在体外对人血清白蛋白 (HSA) 和注射到小鼠后的小鼠血清白蛋白 (MSA) 具有强大的结合能力。通过与 MSA 结合,EV 在不同品系小鼠的不同给药途径后循环时间显著增加。此外,这些工程化的 EV 显示出相当大的淋巴结 (LN) 和实体瘤积累,当使用 EV 进行免疫调节、癌症和/或免疫治疗时,可以利用这一点。当与组织特异性靶向配体结合时,EV 循环时间的延长也可能很重要,并且可能为它们在各种疾病适应症中的治疗用途提供重要益处。