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Anisotropic Biodegradable Lipid Coated Particles for Spatially Dynamic Protein Presentation

机译:各向异性的可生物降解的脂质包覆颗粒用于空间动态蛋白质展示

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摘要

There has been growing interest in the use of particles coated with lipids for applications ranging from drug delivery, gene delivery, and diagnostic imaging to immunoengineering. To date, almost all particles with lipid coatings have been spherical despite emerging evidence that non-spherical shapes can provide important advantages including reduced non-specific elimination and increased target-specific binding. We combine control of core particle geometry with control of particle surface functionality by developing anisotropic, biodegradable ellipsoidal particles with lipid coatings. We demonstrate that these lipid coated ellipsoidal particles maintain advantageous properties of lipid polymer hybrid particles, such as the ability for modular protein conjugation to the particle surface using versatile bioorthogonal ligation reactions. In addition, they exhibit biomimetic membrane fluidity and demonstrate lateral diffusive properties characteristic of natural membrane proteins. These ellipsoidal particles simultaneously provide benefits of non-spherical particles in terms of stability and resistance to non-specific phagocytosis by macrophages as well as enhanced targeted binding. These biomaterials provide a novel and flexible platform for numerous biomedical applications.
机译:人们对使用脂质包裹的颗粒用于药物输送,基因输送,诊断成像到免疫工程的应用越来越感兴趣。迄今为止,尽管有新的证据表明非球形可以提供重要的优势,包括减少非特异性消除和增加靶标特异性结合,但几乎所有具有脂质涂层的颗粒都为球形。通过开发具有脂质涂层的各向异性,可生物降解的椭圆形颗粒,我们将对核心颗粒几何形状的控制与对颗粒表面功能的控制相结合。我们证明,这些脂质涂覆的椭球形颗粒保持了脂质聚合物杂化颗粒的有利性能,例如使用通用的生物正交连接反应使模块化蛋白质与颗粒表面结合的能力。此外,它们表现出仿生膜的流动性,并表现出天然膜蛋白的横向扩散特性。这些椭圆形颗粒在稳定性和对巨噬细胞对非特异性吞噬作用的抵抗以及增强的靶向结合方面同时提供非球形颗粒的益处。这些生物材料为众多生物医学应用提供了一种新颖而灵活的平台。

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