Kovshova Tatyana, Malinovskaya Julia, Kotova Julia, Gorshkova Marina, Vanchugova Lyudmila, Osipova Nadezhda, Melnikov Pavel, Vadekhina Veronika, Nikitin Alexey, Ermolenko Yulia, Gelperina Svetlana
Faculty of Chemical and Pharmaceutical Technologies and Biomedical Preparations, D. Mendeleev University of Chemical Technology of Russia, Miusskaya pl. 9, Moscow 125047, Russia.
Laboratory of Polyelectrolyte Chemistry and Biomedical Polymers, Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Leninsky Prosp. 29, Moscow 119991, Russia.
Biomolecules. 2024 Dec 14;14(12):1601. doi: 10.3390/biom14121601.
The objective of this study was to compare the properties of core-shell nanoparticles with a PLGA core and shells composed of different types of polymers, focusing on their structural integrity. The core PLGA nanoparticles were prepared either through a high-pressure homogenization-solvent evaporation technique or nanoprecipitation, using poloxamer 188 (P188), a copolymer of divinyl ether with maleic anhydride (DIVEMA), and human serum albumin (HSA) as the shell-forming polymers. The shells were formed through adsorption, interfacial embedding, or conjugation. For dual fluorescent labeling, the core- and shell-forming polymers were conjugated with Cyanine5, Cyanine3, and rhodamine B. The nanoparticles had negative zeta potentials and sizes ranging from 100 to 250 nm (measured using DLS) depending on the shell structure and preparation technique. The core-shell structure was confirmed using TEM and fluorescence spectroscopy, with the appearance of FRET phenomena due to the donor-acceptor properties of the labels. All of the shells enhanced the cellular uptake of the nanoparticles in Gl261 murine glioma cells. The integrity of the core-shell structures upon their incubation with the cells was evidenced by intracellular colocalization of the fluorescent labels according to the Manders' colocalization coefficients. This comprehensive approach may be useful for the selection of the optimal preparation method even at the early stages of the core-shell nanoparticle development.
本研究的目的是比较具有聚乳酸-羟基乙酸共聚物（PLGA）核以及由不同类型聚合物组成的壳的核壳纳米颗粒的性质，重点关注其结构完整性。核PLGA纳米颗粒通过高压均质-溶剂蒸发技术或纳米沉淀法制备，使用泊洛沙姆188（P188）、二乙烯基醚与马来酸酐的共聚物（DIVEMA）以及人血清白蛋白（HSA）作为壳形成聚合物。壳通过吸附、界面包埋或共轭形成。对于双荧光标记，核形成聚合物和壳形成聚合物与花菁5、花菁3和罗丹明B共轭。纳米颗粒具有负的zeta电位，尺寸范围为100至250nm（使用动态光散射测量），这取决于壳结构和制备技术。使用透射电子显微镜（TEM）和荧光光谱证实了核壳结构，由于标记物的供体-受体性质出现了荧光共振能量转移（FRET）现象。所有的壳都增强了纳米颗粒在Gl261小鼠胶质瘤细胞中的细胞摄取。根据曼德斯共定位系数，荧光标记物在细胞内的共定位证明了核壳结构与细胞孵育后的完整性。这种综合方法即使在核壳纳米颗粒开发的早期阶段对于选择最佳制备方法也可能是有用的。
