Background

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.

Methods

Thin film hydration method followed by extrusion was used to prepare nanoliposomes, and Dox encapsulation in liposomes was done via 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.

Results

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.

Conclusions

This research showed reduced macrophage uptake, increased blood circulation, and enhanced tumor accumulation of liposomes through SP incorporation on the surface of particles.

中文翻译：

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利用CD47模拟来抑制吞噬作用清除并增强纳米脂质体阿霉素的抗肿瘤功效。

背景

我们假设是否可以通过在脂质体表面掺入CD47模拟肽（Selfeptide：SP）来减轻巨噬细胞对脂质体的吞噬作用。

方法

采用薄膜水化法，然后挤出法制备纳米脂质体，并通过远程加载法将Dox包囊在脂质体中。使用预插入技术制备了具有不同肽密度（每个脂质体表面上有300和600个肽）的SP肽（SP-LD）修饰的脂质体。巨噬细胞系用于比较修饰和未修饰脂质体的细胞摄取。为了进行生物分布研究，荷瘤小鼠接受了制剂，并测量了不同组织中Dox的荧光信号。为了评估抗肿瘤功效，评估了肿瘤大小和存活率。此外，确定了药代动力学参数。

结果

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-脂质体的清除速度较慢。最终，与聚乙二醇化脂质体相比，SP-脂质体高度分布于肿瘤组织，并显着减小了肿瘤的大小并改善了荷瘤小鼠的存活率。

结论

这项研究表明，通过将SP掺入颗粒表面，可以减少巨噬细胞的摄取，增加血液循环并增强脂质体在肿瘤中的蓄积。