Background

Nanoparticles that actively target tissues, with ligands attached at the extremity of polyethylene glycol (PEG) spacer, are a promising strategy to enhance target cell specificity and internalization. However, the interplay between the targeting ligands and the adjacent ligand-free PEG remains poorly understood.

Research design and methods

Experimentally, liposomes containing active folate ligands were firstly formulated and the optimum amount of ligand that yields the highest foam cell uptake was determined. Subsequently, ligand-free PEG was incorporated, and the effects of PEG lengths and concentrations on foam cell uptake were evaluated after the nanoparticles were incubated in human serum for 90 min.

Results

It was demonstrated that the targeting efficiency progressively decreased and was eventually annulled as PEG-to-ligand ratio was increased, with loss of targeting effect occurring at PEG-to-ligand ratio of >2 for PEG 750, >0.5 for PEG 2000 and <0.5 for PEG 5000.

Conclusions

This work demonstrates that PEG-to-ligand ratio and serum coating on nanoparticle surface are both important features to be considered in the design of active targeting nanocarriers. This work also supports the development of novel active targeting nanotherapies for atherosclerosis.

中文翻译：

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纳米脂质体对动脉粥样硬化泡沫细胞的靶向效率：聚乙二醇与配体的比率效应。

背景

主动靶向组织的纳米颗粒具有在聚乙二醇（PEG）间隔基末端连接的配体，是一种增强靶细胞特异性和内在化的有前途的策略。但是，靶向配体与相邻的不含配体的PEG之间的相互作用仍然知之甚少。

研究设计与方法

实验上，首先配制了含有活性叶酸配体的脂质体，并确定了产生最高泡沫细胞摄取量的最佳配体量。随后，掺入不含配体的PEG，将纳米颗粒在人血清中孵育90分钟后，评估PEG长度和浓度对泡沫细胞摄取的影响。

结果

事实证明，随着PEG与配体的比率增加，靶向效率逐渐降低，最终被废除，对于PEG 750的PEG与配体的比率> 2，对于PEG 2000大于> 0.5且< PEG 5000为0.5。

结论

这项工作表明，PEG与配体的比率以及纳米颗粒表面的血清包被都是设计活性靶向纳米载体时要考虑的重要特征。这项工作还支持用于动脉粥样硬化的新型主动靶向纳米疗法的开发。