Gheibi Hayat Seyed Mohammad, Jaafari Mahmoud R, Hatamipour Mahdi, Jamialahmadi Tannaz, Sahebkar Amirhossein
Department of Medical Biotechnology, Faculty Medicine, Mashhad University of Medical Sciences , Mashhad, Iran.
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences , Mashhad, Iran.
Expert Opin Drug Deliv. 2020 Jul;17(7):1049-1058. doi: 10.1080/17425247.2020.1772749. Epub 2020 Jun 16.
We hypothesized if phagocytosis of liposomes by macrophages could be mitigated through incorporation of a CD47 mimicry peptide (Self peptide: SP) on the surface of liposomes.
Thin film hydration method followed by extrusion was used to prepare nanoliposomes, and Dox encapsulation in liposomes was done remote-loading method. Decorated liposomes with SP peptide (SP-LD) at different peptide densities (300 and 600 peptides on the surface of each liposome) were prepared using a pre-insertion technique. Macrophage cell lines were used to compare the cellular uptake of decorated and unmodified liposomes. For biodistribution studies, tumor-bearing mice received the preparations, and fluorescence signals of Dox in different tissues were measured. To evaluate anti-tumor efficacy, tumor size and survival rates were assessed. Also, pharmacokinetic parameters were determined.
Compared with PEGylated liposomes, uptake by macrophages was largely decreased when SP was incorporated on liposomes. Following intravenous injection, SP-liposomes were cleared more slowly compared with PEGylated liposomes. Eventually, SP-liposomes were highly distributed to tumor tissues compared with PEGylated liposomes, and significantly reduced tumor size and improved the survival of tumor-bearing mice.
This research showed reduced macrophage uptake, increased blood circulation, and enhanced tumor accumulation of liposomes through SP incorporation on the surface of particles.
我们假设通过在脂质体表面掺入CD47模拟肽（自身肽：SP），巨噬细胞对脂质体的吞噬作用是否可以减轻。
采用薄膜水化法结合挤压法制备纳米脂质体，并采用远程加载法将阿霉素包封于脂质体中。使用预插入技术制备了不同肽密度（每个脂质体表面有300和600个肽）的SP肽修饰脂质体（SP-LD）。使用巨噬细胞系比较修饰脂质体和未修饰脂质体的细胞摄取情况。对于生物分布研究，给荷瘤小鼠注射制剂，并测量不同组织中阿霉素的荧光信号。为了评估抗肿瘤疗效，评估肿瘤大小和存活率。此外，还测定了药代动力学参数。
与聚乙二醇化脂质体相比，当SP掺入脂质体时，巨噬细胞的摄取量大大降低。静脉注射后，与聚乙二醇化脂质体相比，SP脂质体的清除速度更慢。最终，与聚乙二醇化脂质体相比，SP脂质体在肿瘤组织中的分布更高，并显著减小肿瘤大小，提高荷瘤小鼠的存活率。
本研究表明，通过在颗粒表面掺入SP，可减少巨噬细胞摄取，增加血液循环，并增强脂质体在肿瘤中的蓄积。
