Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Sci Adv. 2020 Feb 7;6(6):eaay7952. doi: 10.1126/sciadv.aay7952. eCollection 2020 Feb.
Microscale hydrogels consisting of macromolecular networks in aqueous continuous phases have received increasing attention because of their potential use in tissue engineering, cell encapsulation and for the storage and release of cargo molecules. However, for applications targeting intracellular delivery, their micrometer-scale size is unsuitable for effective cellular uptake. Nanoscale analogs of such materials are thus required for this key area. Here, we describe a microfluidics/nanofluidics-based strategy for generating monodisperse nanosized water-in-oil emulsions with controllable sizes ranging from 2500 ± 110 nm down to 51 ± 6 nm. We demonstrate that these nanoemulsions can act as templates to form protein nanogels stabilized by supramolecular fibrils from three different proteins. We further show that these nanoparticles have the ability to penetrate mammalian cell membranes and deliver intracellular cargo. Due to their biocompatibility and lack of toxicity, natural protein-based nanoparticles present advantageous characteristics as vehicles for cargo molecules in the context of pharmaceutical and biomedical applications.
由于在组织工程、细胞包封以及货物分子的储存和释放方面的潜在应用，由水连续相中的高分子网络组成的微尺度水凝胶受到了越来越多的关注。然而，对于针对细胞内递药的应用，其微米级的尺寸不利于细胞的有效摄取。因此，此类材料的纳米级类似物是这一关键领域所必需的。在这里，我们描述了一种基于微流控/纳流控的策略，用于生成单分散的纳米级油包水乳状液，其尺寸可控，范围从 2500±110nm 缩小至 51±6nm。我们证明，这些纳米乳液可以作为模板，形成由三种不同蛋白质的超分子纤维稳定的蛋白质纳米凝胶。我们进一步表明，这些纳米颗粒具有穿透哺乳动物细胞膜并递送细胞内货物的能力。由于其生物相容性和缺乏毒性，天然蛋白质纳米颗粒作为药物和生物医学应用中货物分子载体具有有利的特性。
