Surface-grafted polyethylene glycol conformation impacts the transport of PEG-functionalized liposomes through a tumour extracellular matrix model
Surface-grafted polyethylene glycol conformation impacts the transport of PEG-functionalized liposomes through a tumour extracellular matrix model
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DOI：
10.1039/c7ra13438j
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发表时间：
2018-01-01
期刊：
影响因子：
3.9
通讯作者：
Cramb, David T.
中科院分区：
文献类型：
--
作者：
Labouta, Hagar I.;Gomez-Garcia, M. Juliana;Cramb, David T.
表面聚乙二醇化对纳米颗粒通过细胞外基质(ECM)转运的影响是肿瘤靶向成功的重要决定因素。将不同比例的聚乙二醇接枝脂(占总脂含量的2.5%、5%和10%)与不同相对分子质量(1000、2000和5000Da)的聚乙二醇酯(PEG1000、2000和5000Da)混合，制备了荧光隐形脂质体(DOPC)。使用胶原蛋白基质对ECM进行建模。分别用荧光相关光谱(FCS)和共聚焦显微镜跟踪聚乙二醇化脂质体在胶原基质上的黏附和转运动力学。用广义最小二乘回归分析了聚乙二醇分子量、表面密度和构象与脂质体在胶原水凝胶中15小时的转运之间的时间相关性。聚乙二醇单分子构象决定了脂质体与胶原水凝胶的相互作用及其转运行为。有趣的是，具有蘑菇状聚乙二醇构象的脂质体聚集在胶原水凝胶的界面上，形成致密的脂质体前沿，扩散到水凝胶中的距离较短。另一方面，具有致密的刷状构象的脂质体与胶原水凝胶的相互作用程度较小，并扩散到较长的距离。总之，更好地理解了聚乙二醇表面涂层在模型ECM基质中作为传输调节剂的作用。这一知识将改进未来脂质体药物载体系统的设计。
The effect of surface PEGylation on nanoparticle transport through an extracellular matrix (ECM) is an important determinant for tumor targeting success. Fluorescent stealth liposomes (base lipid DOPC) were prepared incorporating different proportions of PEG-grafted lipids (2.5, 5 and 10% of the total lipid content) for a series of PEG molecular weights (1000, 2000 and 5000 Da). The ECM was modelled using a collagen matrix. The kinetics of PEGylated liposome adhesion to and transport in collagen matrices were tracked using fluorescence correlation spectroscopy (FCS) and confocal microscopy, respectively. Generalized least square regressions were used to determine the temporal correlations between PEG molecular weight, surface density and conformation, and the liposome transport in a collagen hydrogel over 15 hours. PEG conformation determined the interaction of liposomes with the collagen hydrogel and their transport behaviour. Interestingly, liposomes with mushroom PEG conformation accumulated on the interface of the collagen hydrogel, creating a dense liposomal front with short diffusion distances into the hydrogels. On the other hand, liposomes with dense brush PEG conformation interacted to a lesser extent with the collagen hydrogel and diffused to longer distances. In conclusion, a better understanding of PEG surface coating as a modifier of transport in a model ECM matrix has resulted. This knowledge will improve design of future liposomal drug carrier systems.