Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
ACS Nano. 2010 Mar 23;4(3):1671-9. doi: 10.1021/nn901433u.
A key challenge in the synthesis of multicomponent nanoparticles (NPs) for therapy or diagnosis is obtaining reproducible monodisperse NPs with a minimum number of preparation steps. Here we report the use of microfluidic rapid mixing using hydrodynamic flow focusing in combination with passive mixing structures to realize the self-assembly of monodisperse lipid-polymer and lipid-quantum dot (QD) NPs in a single mixing step. These NPs are composed of a polymeric core for drug encapsulation or a QD core for imaging purposes, a hydrophilic polymeric shell, and a lipid monolayer at the interface of the core and the shell. In contrast to slow mixing of lipid and polymeric solutions, rapid mixing directly results in formation of homogeneous NPs with relatively narrow size distribution that obviates the need for subsequent thermal or mechanical agitation for homogenization. We identify rapid mixing conditions that result in formation of homogeneous NPs and show that self-assembly of polymeric core occurs independent of the lipid component, which only provides stability against aggregation over time and in the presence of high salt concentrations. Physicochemical properties of the NPs including size (35-180 nm) and zeta potential (-10 to +20 mV in PBS) are controlled by simply varying the composition and concentration of precursors. This method for preparation of hybrid NPs in a single mixing step may be useful for combinatorial synthesis of NPs with different properties for imaging and drug delivery applications.
在合成用于治疗或诊断的多组分纳米粒子（NPs）时，一个关键的挑战是获得具有最小制备步骤的重现性单分散 NPs。在这里，我们报告了使用微流控快速混合，结合被动混合结构，在单个混合步骤中实现单分散脂质-聚合物和脂质-量子点（QD）NPs 的自组装。这些 NPs 由用于药物包封的聚合物核、用于成像的 QD 核、亲水性聚合物壳和核与壳之间的脂质单层组成。与脂质和聚合物溶液的缓慢混合相比，快速混合直接导致形成相对较窄尺寸分布的均匀 NPs，从而无需后续的热或机械搅拌来实现均匀化。我们确定了导致形成均匀 NPs 的快速混合条件，并表明聚合物核的自组装独立于脂质成分，脂质成分仅提供了随着时间的推移和在高盐浓度下防止聚集的稳定性。NPs 的物理化学性质包括尺寸（35-180nm）和 Zeta 电位（PBS 中为-10 至+20mV），通过简单地改变前体的组成和浓度来控制。这种在单个混合步骤中制备杂化 NPs 的方法可能对用于成像和药物输送应用的具有不同性质的 NPs 的组合合成有用。
