Department of Mechanical Engineering and Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA.
Nanoscale. 2016 Aug 21;8(31):14821-35. doi: 10.1039/c6nr04134e. Epub 2016 Jul 25.
Herein a new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the formation of a CPLS nanoparticle. The self-assembly process is found to be sensitive to the grafting density and molecular weight of the tethered PEG chains, as well as the amount of free lipids added. At low grafting densities the assembly of CPLS nanoparticles cannot be accomplished. As demonstrated by simulations, a lipid bud/vesicle can be formed on the surface when an excess amount of free lipids is added at high grafting density. Therefore, the CPLS nanoparticles can only be formed under appropriate conditions of both PEG and free lipids. The CPLS nanoparticle has been recognized to be able to store a large quantity of water molecules, particularly with high molecular weight of PEG chains, indicating its capacity for carrying hydrophilic molecules such as therapeutic biomolecules or imaging agents. Under identical size and surface chemistry conditions of a liposome, it has been observed that the CPLS particle can be more efficiently wrapped by the lipid membrane, indicating its potential for a greater efficiency in delivering its hydrophilic cargo. As a proof-of-concept, the experimental realization of CPLS nanoparticles is explicitly demonstrated in this study. To test the capacity of the CPLS to store small molecule cargo a hydrophilic dye was successfully encapsulated in the particles' water soluble layer. The results of this study show the power and potential of simulation-driven approaches for guiding the design of more efficient nanomaterial delivery platforms.
在此提出并通过大规模粗粒化分子动力学模拟对一种新的多功能制剂进行了研究，称为核-聚乙二醇-脂质壳（CPLS）纳米颗粒。以接枝有聚乙二醇（PEG）链的 PEG 化核作为起始构型，PEG 链的自由端通过共价键与脂质分子（脂质头）结合。在添加游离脂质时，由于脂质尾部的疏水性，在 PEG 化颗粒核的表面形成完整的脂质双层，导致 CPLS 纳米颗粒的形成。自组装过程对接枝的 PEG 链的接枝密度和分子量以及添加的游离脂质的量敏感。在低接枝密度下，CPLS 纳米颗粒的组装无法完成。模拟表明，当在高接枝密度下添加过量的游离脂质时，可以在表面上形成脂质芽/囊泡。因此，只有在适当的 PEG 和游离脂质条件下才能形成 CPLS 纳米颗粒。CPLS 纳米颗粒已被证明能够储存大量水分子，尤其是具有高分子量的 PEG 链，表明其携带治疗生物分子或成像剂等亲水分子的能力。在脂质体相同的大小和表面化学条件下，观察到 CPLS 颗粒可以更有效地被脂质膜包裹，表明其在更有效地输送亲水性货物方面具有潜力。作为概念验证，本研究明确地展示了 CPLS 纳米颗粒的实验实现。为了测试 CPLS 储存小分子货物的能力，成功地将亲水性染料封装在颗粒的水溶性层中。该研究的结果表明，模拟驱动方法在指导更有效的纳米材料输送平台的设计方面具有强大的潜力。
