Department of Health Technology, Technical University of Denmark, Building 345C, 2800 Kgs. Lyngby, Denmark.
Department of Opthalmology, Rigshospitalet, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Int J Pharm. 2020 Oct 15;588:119715. doi: 10.1016/j.ijpharm.2020.119715. Epub 2020 Aug 1.
Targeting nanocarrier drug delivery systems, that deliver drug payloads to the site of disease action, are frequently viewed as the future of nanocarrier based therapies but have struggled to breakthrough to the clinic in comparison to non-targeting counterparts. Using unilamellar liposomes as model nanocarriers, we show that cell targeting strategy (electrostatic, ligand and antigen) influences both the intracellular fate of the liposomes and the corresponding efficacy of the loaded drug, doxorubicin, in endothelial cells. We show that increased liposome uptake by cells does not translate to improved efficacy in this scenario but that liposome intracellular trafficking, particularly distribution between recycling endosomes and lysosomes, influences in vitro efficacy. Choosing targeting strategies that promote desired nanocarrier intracellular trafficking may be a viable strategy to enhance the in vivo efficacy of drug delivery systems.
靶向纳米载体药物递送系统，将药物有效载荷递送到疾病作用部位，通常被视为基于纳米载体治疗的未来，但与非靶向物相比，它们在向临床突破方面一直面临困难。我们使用单层脂质体作为模型纳米载体，表明细胞靶向策略（静电、配体和抗原）会影响脂质体的细胞内命运以及负载药物阿霉素在血管内皮细胞中的相应疗效。我们表明，细胞摄取的脂质体增加并不一定能提高这种情况下的疗效，而是脂质体的细胞内运输，特别是在再循环内体和溶酶体之间的分布，会影响体外疗效。选择能促进理想的纳米载体细胞内运输的靶向策略，可能是增强药物递送系统体内疗效的可行策略。
