Interdisciplinary Biological Sciences, Northwestern University, Evanston, IL, USA.
Department of Biomedical Engineering and Northwestern University, Evanston, IL, USA.
J Control Release. 2017 Sep 28;262:91-103. doi: 10.1016/j.jconrel.2017.07.026. Epub 2017 Jul 20.
Flash nanoprecipitation (FNP) has proven to be a powerful tool for the rapid and scalable assembly of solid-core nanoparticles from block copolymers. The process can be performed using a simple confined impingement jets mixer and provides an efficient and reproducible method of loading micelles with hydrophobic drugs. To date, FNP has not been applied for the fabrication of complex or vesicular nanoarchitectures capable of encapsulating hydrophilic molecules or bioactive protein therapeutics. Here, we present FNP as a single customizable method for the assembly of bicontinuous nanospheres, filomicelles and vesicular, multilamellar and tubular polymersomes from poly(ethylene glycol)-bl-poly(propylene sulfide) block copolymers. Multiple impingements of polymersomes assembled via FNP were shown to decrease vesicle diameter and polydispersity, allowing gram-scale fabrication of monodisperse polymersomes within minutes. Furthermore, we demonstrate that FNP supports the simultaneous loading of both hydrophobic and hydrophilic molecules respectively into the polymersome membrane and aqueous lumen, and encapsulated enzymes were found to be released and remain active following vesicle lysis. As an example application, theranostic polymersomes were generated via FNP that were dual loaded with the immunosuppressant rapamycin and a fluorescent dye to link targeted immune cells with the elicited immunomodulation of T cells. By expanding the capabilities of FNP, we present a rapid, scalable and reproducible method of nanofabrication for a wide range of nanoarchitectures that are typically challenging to assemble and load with therapeutics for controlled delivery and theranostic strategies.
闪式纳米沉淀（FNP）已被证明是一种从嵌段共聚物快速且规模化制备核壳型纳米颗粒的有力工具。该方法可使用简单的受限撞击射流混合器来完成，提供了一种高效且可重现的方法，可将疏水性药物载入胶束中。迄今为止，FNP 尚未应用于制备能够包封亲水性分子或生物活性蛋白治疗剂的复杂或囊泡型纳米结构。在这里，我们提出 FNP 可作为一种单一的可定制方法，用于从聚乙二醇-b-聚（丙硫醚）嵌段共聚物组装双连续纳米球、丝状胶束和囊泡、多层和管状聚合物囊泡。通过 FNP 组装的聚合物囊泡的多次撞击可减小囊泡的直径和多分散性，使在几分钟内可实现克级规模的单分散聚合物囊泡的制备。此外，我们证明 FNP 支持分别将疏水性和亲水性分子同时载入聚合物囊泡的膜和水腔中，并且包封的酶在囊泡裂解后被释放并保持活性。作为一个应用实例，通过 FNP 生成了载有免疫抑制剂雷帕霉素和荧光染料的治疗性聚合物囊泡，以将靶向免疫细胞与 T 细胞的免疫调节作用联系起来。通过扩展 FNP 的功能，我们提出了一种快速、可扩展且可重现的纳米制造方法，可用于制备各种纳米结构，这些纳米结构通常难以组装和载入治疗药物，以用于控制释放和治疗学策略。
