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首页> 外文期刊>BMC Biophysics >GPMVs in variable physiological conditions: could they be used for therapy delivery?
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GPMVs in variable physiological conditions: could they be used for therapy delivery?

机译：可变生理条件下的GPMV：可用于治疗吗？

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Cell based carriers are increasingly recognized as a good system for cargo delivery to cells. One of the reasons is their biocompatibility and low toxicity compared to artificial systems. Giant plasma membrane vesicles (GPMV) derive from the cell plasma membrane. Thus they offer the closest approximation to it, which makes them good candidates for potential drug delivery systems. To evaluate the applicability of GPMVs as carriers, we analyzed their basic biophysical properties to test their robustness in the face of changeable physiological conditions, as well as their ability to translocate across the membrane into cells. GPMVs formed from human umbilical vein endothelial cells (HUVEC) sustain a drastic osmotic challenge (50–500 mOsmoL/kg) unlike giant unilamelar vesicles (GUVs). In hyper-osmotic solutions the average volume decreases and membrane invaginations form, while in the hypo-osmolar buffer the volume of GPMVs increases and these changes were not reversible. The membranes of flaccid GPMVs started to wrinkle unevenly giving rise to buds after exposure to lipopolysaccharide (LPS). The shape changes in GUVs are reversible in contrast to GPMVs after LPS removal. GPMVs exposed to fluorescent LPS exhibited a signal that remained visible in some GPMVs even after LPS removal, which was never the case with GUVs. Calcein penetrated both into GUVs and GPMVs, however after the removal from the bulk solution some of the GPMVs still exhibited very bright signal, while in GUVs only a weak fluorescent signal was detected. We could also see that practically all GPMVs incorporated dextran initially, but after the dextran solution was changed with the initial non-fluorescent solution it remained only in 20% of them. The majority of HUVEC cells displayed a fluorescent signal after the incubation with GPMVs that contained fluorescently labeled dextran. Our findings indicate that GPMVs behave quite differently from artificially made giant phospholipid vesicles and the changes induced by the different treatments we subjected them to are not reversible. We also demonstrate that different substances can be both loaded into them and delivered into cells, so GPMVs may be of potential use as cargo/therapy delivery systems.
机译：基于单元的运载工具越来越被认为是一种将货物运送到单元的好系统。原因之一是它们与人工系统相比具有生物相容性和低毒性。巨质膜囊泡（GPMV）来源于细胞质膜。因此，它们提供了与之最接近的近似值，这使其成为潜在药物输送系统的良好候选者。为了评估GPMV作为载体的适用性，我们分析了它们的基本生物物理特性，以测试其在变化的生理条件下的坚固性，以及它们跨膜转运进入细胞的能力。与巨大的单层囊泡（GUV）不同，由人脐静脉内皮细胞（HUVEC）形成的GPMV承受着剧烈的渗透挑战（50–500 mOsmoL / kg）。在高渗溶液中，平均体积减少，形成膜内陷，而在低渗缓冲液中，GPMV的体积增加，并且这些变化不可逆。暴露于脂多糖（LPS）后，松弛的GPMVs的膜开始不均匀地起皱，并产生芽。与LPS去除后的GPMV相比，GUV的形状变化是可逆的。暴露于荧光LPS的GPMV表现出的信号即使在去除LPS后仍在某些GPMV中仍然可见，而GUV则从来没有。钙黄绿素同时渗透到GUV和GPMV中，但是从本体溶液中去除后，某些GPMV仍显示出非常明亮的信号，而在GUV中仅检测到微弱的荧光信号。我们还可以看到，实际上所有GPMV最初都掺入了葡聚糖，但是在用最初的非荧光溶液更换了葡聚糖溶液之后，它仅保留其中的20％。与含有荧光标记葡聚糖的GPMV孵育后，大多数HUVEC细胞显示出荧光信号。我们的发现表明，GPMVs与人工制造的巨大磷脂囊泡的行为有很大不同，并且我们接受它们的不同处理所引起的变化是不可逆的。我们还证明了不同的物质既可以加载到其中，也可以传递到细胞中，因此GPMV可能用作货物/治疗传递系统。

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