文献：阐明脂质体破裂的驱动力：外部扰动和化学亲和力

链接：https://pubs.acs.org/doi/abs/10.1021/la300127m

作者：王曦，马修·M·辛德尔，王思文，雷吉娜·拉根

摘要：

通过反义寡脱氧核苷酸 (AS-ODN) 或小干扰 RNA (siRNA) 疗法进行选择性基因抑制有望*传统药物无法治愈的疾病。然而，反义疗法由于在生理液中的稳定性差和细胞内摄取有限而受到阻碍。为了解决这些问题，我们实验室开发了一种配体靶向和空间稳定的纳米颗粒制剂。人类肺癌细胞通常过表达 σ 受体，因此可以用特定配体（例如茴香酰胺）进行靶向*。将针对人类生存素的 AS-ODN 或 siRNA 与载体 DNA（小牛胸腺 DNA）混合，然后与鱼精蛋白（一种带高正电荷的肽）复合。

将所得颗粒用由 DOTAP 和胆固醇（摩尔比 1:1）组成的阳离子脂质体包被，以获得 LPD（脂质体-聚阳离子-DNA）纳米颗粒。然后，通过后插入法将预制的LPD纳米粒子与DSPE-PEG-茴香酰胺（我们实验室早期开发的一种PEG化配体脂质）一起孵育，引入配体靶向性和空间稳定性。同时制备了DSPE-PEG包覆的非靶向纳米粒子作为对照。

通过Survivin mRNA下调、Survivin蛋白下调、引发*细胞凋亡的能力、*细胞生长抑制以及处理后的*细胞对*癌药物的化学增敏作用来测定纳米粒子的反义活性。我们发现，PEG化纳米粒子的*细胞递送和反义活性是序列依赖性的，并且依赖于茴香酰胺配体的存在。靶向PEG化纳米粒子对寡核苷酸的摄取可能会被过量的游离配体竞争。我们的结果表明，配体靶向和空间稳定的纳米粒子可以选择性地将 AS-ODN 和 siRNA 递送到肺癌细胞中进行*。

Abstract

Abstract Image

Atomic force microscopy (AFM) studies under aqueous buffer probed the role of chemical affinity between liposomes, consisting of large unilamellar vesicles, and substrate surfaces in driving vesicle rupture and tethered lipid bilayer membrane (tLBM) formation on Au surfaces. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-2000-N-[3-(2-pyridyldithio) propionate] (DSPE-PEG-PDP) was added to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles to promote interactions via Au–thiolate bond formation. Forces induced by an AFM tip leading to vesicle rupture on Au were quantified as a function of DSPE-PEG-PDP composition with and without osmotic pressure. The critical forces needed to initiate rupture of vesicles with 2.5, 5, and 10 mol % DSPE-PEG-PDP are approximately 1.1, 0.8, and 0.5 nN, respectively. The critical force needed for tLBM formation decreases from 1.1 nN (without osmotic pressure) to 0.6 nN (with an osmotic pressure due to 5 mM of CaCl2) for vesicles having 2.5 mol % DSPE-PEG-PDP. Forces as high as 5 nN did not lead to LBM formation from pure POPC vesicles on Au. DSPE-PEG-PDP appears to be important to anchor and deform vesicles on Au surfaces. This study demonstrates how functional lipids can be used to tune vesicle–surface interactions and elucidates the role of vesicle–substrate interactions in vesicle rupture.

西安齐岳生物提供相关产品：

DSPE-PEG-ferrocene

DSPE-PEG-WGA

DSPE-PEG-Streptavidin

DSPE-PEG-BSA

DSPE-PEG-Lysozyme

DSPE-PEG-PLL

DSPE-PEG-Heparin

DSPE-PEG-Insulin

DSPE-PEG-Lectins

DSPE-PEG-lactoferrin

以上文章内容来源各类期刊或文献，如有侵权请联系我们删除！