Drug-loaded liposomes are the most successful nanomedicine to date, with multiple FDA-approved systems for a myriad of diseases. While liposome circulation time in blood and retention in tissues have been studied in detail, the structural fate of liposomes—and nanoparticles in general—in the body has not been extensively investigated. Here, we explore the interactions of liposomes with synthetic and natural hydrogel materials to understand how the natural extracellular matrix influences liposome structural characteristics. Small angle X-ray scattering, confocal microscopy, and cryogenic transmission electron microscopy data demonstrate that poly(ethylene glycol) (PEG), gelatin, alginate, and Matrigel® hydrogels cause 200 nm liposomes of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) to transform into micrometer-sized aggregates. These aggregates are composed of multilamellar vesicles around 100 nm in diameter with a mean interlamellar separation of 5.5 nm. Protecting the liposomes with a corona of PEG damps this restructuring effect, making the multilamellar vesicles less stable. We attribute this unilamellar to multilamellar transition to an osmotic driving force from the hydrogel environment. This lipid restructuring has broad ramifications in the design and use of nanomedicines, and in understanding the fate and function of natural lipid-based materials within the tissue microenvironment.

中文翻译：

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脂质纳米颗粒在细胞外基质中的结构命运†

载药脂质体是迄今为止最成功的纳米药物，具有多种FDA批准的多种疾病治疗系统。尽管已经详细研究了脂质体在血液中的循环时间和在组织中的保留时间，但尚未广泛研究体内脂质体（以及一般而言的纳米颗粒）的结构命运。在这里，我们探索脂质体与合成和天然水凝胶材料的相互作用，以了解天然细胞外基质如何​​影响脂质体的结构特征。小角X射线散射，共聚焦显微镜和低温透射电子显微镜数据表明，聚乙二醇（PEG），明胶​​，藻酸盐和Matrigel®水凝胶可导致200 nm的1,2-二油酰基-sn-甘油脂质体-3-磷酸胆碱（DOPC）转化为微米级的聚集体。这些聚集体由直径约100 nm的多层囊泡组成，平均层间间距为5.5 nm。用PEG电晕保护脂质体会减弱这种重组效果，从而使多层囊泡的稳定性降低。我们将此单层归因于多层过渡到来自水凝胶环境的渗透驱动力。这种脂质重组在纳米药物的设计和使用以及在组织微环境中了解天然脂质基材料的命运和功能方面具有广泛的意义。