Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21231, USA.
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Acta Biomater. 2018 May;72:228-238. doi: 10.1016/j.actbio.2018.03.056. Epub 2018 Apr 7.
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.
The research reported here documents the ability of non-spherical polymeric particles to be coated with lipids to form anisotropic biomimetic particles. In addition, we demonstrate that these lipid-coated biodegradable polymeric particles can be conjugated to a wide variety of biological molecules in a "click-like" fashion. This is of interest due to the multiple types of cellular mimicry enabled by this biomaterial based technology. These features include mimicry of the highly anisotropic shape exhibited by cells, surface presentation of membrane bound protein mimetics, and lateral diffusivity of membrane bound substrates comparable to that of a plasma membrane. This platform is demonstrated to facilitate targeted cell binding while being resistant to non-specific cellular uptake. Such a platform could allow for investigations into how physical parameters of a particle and its surface affect the interface between biomaterials and cells, as well as provide biomimetic technology platforms for drug delivery and cellular engineering.
人们对使用涂有脂质的颗粒的兴趣日益浓厚，这些颗粒的应用范围从药物输送、基因输送、诊断成像到免疫工程。迄今为止，尽管有新的证据表明非球形形状可以提供重要的优势，包括减少非特异性消除和增加靶向特异性结合，但几乎所有带有脂质涂层的颗粒都是球形的。我们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，将控制核心颗粒几何形状与控制颗粒表面功能结合起来。我们证明，这些涂有脂质的椭圆形颗粒保持了脂质聚合物杂化颗粒的有利特性，例如使用多功能生物正交连接反应将模块化蛋白质缀合到颗粒表面的能力。此外，它们表现出仿生膜流动性，并表现出与天然膜蛋白特征性的侧向扩散特性。这些椭圆形颗粒同时提供了非球形颗粒在稳定性和抵抗巨噬细胞非特异性吞噬以及增强靶向结合方面的优势。这些生物材料为许多生物医学应用提供了一个新颖而灵活的平台。
这里报道的研究记录了非球形聚合物颗粒被涂覆脂质以形成各向异性仿生颗粒的能力。此外，我们证明，这些可生物降解的涂有脂质的聚合物颗粒可以以“点击式”方式与各种生物分子连接。这是因为这种基于生物材料的技术可以实现多种类型的细胞模拟。这些特性包括细胞表现出的高度各向异性形状的模拟、膜结合蛋白模拟物的表面呈现以及膜结合底物的侧向扩散性与质膜相当。该平台被证明可以促进靶向细胞结合，同时抵抗非特异性细胞摄取。这样的平台可以允许研究颗粒的物理参数及其表面如何影响生物材料与细胞之间的界面，以及为药物输送和细胞工程提供仿生技术平台。
