Butler Kimberly S, Durfee Paul N, Theron Christophe, Ashley Carlee E, Carnes Eric C, Brinker C Jeffrey
Center for Micro-Engineered Materials, The University of New Mexico, Albuquerque, NM, 87131, USA.
Department of Chemical and Biological Engineering, The University of New Mexico, Albuquerque, NM, 87131, USA.
Small. 2016 Apr 27;12(16):2173-85. doi: 10.1002/smll.201502119. Epub 2016 Jan 18.
Mesoporous silica nanoparticle-supported lipid bilayers, termed 'protocells,' represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single 'magic bullet'. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the mesoporous silica nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.
介孔二氧化硅纳米颗粒负载的脂质双层，即所谓的“原始细胞”，是一类具有潜在变革性的治疗和诊疗递送载体。靶向药物递送领域面临着诸多挑战，无法通过单一的“神奇子弹”来解决。因此，原始细胞被设计成一个由可互换的生物相容性组件组成的模块化平台。介孔二氧化硅核心具有可变的大小和形状以指导生物分布，以及可控的孔径和表面化学性质以容纳各种货物。封装的负载脂质双层可以用靶向和运输配体以及聚乙二醇（PEG）进行修饰，以实现选择性结合、货物的内体逃逸、防止药物外排和高效的治疗递送，同时保持体内胶体稳定性。本综述描述了该平台的各个组件，包括介孔二氧化硅纳米颗粒核心和负载脂质双层，它们（通过多种技术）组装成原始细胞，以及基于体外和体内研究的原始细胞的综合性能，通常是协同性能，包括生物相容性和毒性评估。最后，对原始细胞主题的许多新兴变体以及原始细胞研究的未来方向进行了评论。
