Rahmani Sahar, Ashraf Sumaira, Hartmann Raimo, Dishman Acacia F, Zyuzin Mikhail V, Yu Chris K J, Parak Wolfgang J, Lahann Joerg
Biointerfaces Institute, University of Michigan Ann Arbor MI 48109.
Biomedical Engineering University of Michigan Ann Arbor MI 48109.
Bioeng Transl Med. 2016 Jun 20;1(1):82-93. doi: 10.1002/btm2.10010. eCollection 2016 Mar.
Engineering the physical properties of particles, especially their size, is an important parameter in the fabrication of successful carrier systems for the delivery of therapeutics. Here, various routes were explored for the fabrication of particles in the nanosize regime. It was demonstrated that the use of a charged species and/or solvent with high dielectric constant can influence the size and distribution of particles, with the charged species having a greater effect on the size of the particles and the solvent a greater effect on the distribution of the particles. In addition to the fabrication of nanoparticles, their fractionation into specific size ranges using centrifugation was also investigated. The in vitro particle uptake and intracellular transport of these nanoparticles was studied as a function of size and incubation period. The highest level of intralysosomal localization was observed for the smallest nanoparticle group (average of 174 nm), followed by the groups with increasing sizes (averages of 378 and 575 nm), most likely due to the faster endosomal uptake of smaller particles. In addition, the internalization of nanoparticle clusters and number of nanoparticles per cell increased with longer incubation periods. This work establishes a technological approach to compartmentalized nanoparticles with defined sizes. This is especially important as relatively subtle differences in size can modulate cell uptake and determine intercellular fate. Future work will need to address the role of specific targeting ligands on cellular uptake and intracellular transport of compartmentalized nanoparticles.
调控颗粒的物理性质，尤其是其尺寸，是制备成功的治疗药物递送载体系统的一个重要参数。在此，探索了多种制备纳米级颗粒的途径。结果表明，使用带电物质和/或高介电常数的溶剂会影响颗粒的尺寸和分布，其中带电物质对颗粒尺寸的影响更大，而溶剂对颗粒分布的影响更大。除了制备纳米颗粒外，还研究了使用离心法将其分馏到特定尺寸范围。研究了这些纳米颗粒的体外颗粒摄取和细胞内转运与尺寸和孵育时间的关系。观察到最小纳米颗粒组（平均174nm）的溶酶体内定位水平最高，其次是尺寸逐渐增大的组（平均378和575nm），这很可能是由于较小颗粒的内体摄取更快。此外，纳米颗粒簇的内化和每个细胞中纳米颗粒的数量随孵育时间延长而增加。这项工作建立了一种制备具有确定尺寸的分隔纳米颗粒的技术方法。这一点尤为重要，因为尺寸上相对细微的差异会调节细胞摄取并决定细胞间命运。未来的工作需要研究特定靶向配体在分隔纳米颗粒的细胞摄取和细胞内转运中的作用。
