Pillai Gopikrishna J, Greeshma M M, Menon Deepthy
Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India.
Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India.
Colloids Surf B Biointerfaces. 2015 Dec 1;136:1058-66. doi: 10.1016/j.colsurfb.2015.10.047. Epub 2015 Nov 1.
The initial interactions of nanoparticles with biomolecules have a great influence on its toxicity, efficacy, biodistribution and clearance. The present work is an attempt to understand the impact of surface charge of polymeric nanoparticles on its plasma protein and cellular interactions. Negative, near-neutral and positively charged poly(lactic-co-glycolic acid) [PLGA] nanoparticles were prepared using casein, poly(vinyl alcohol) and poly(ethylene imine) respectively, as surface stabilizers. A significant temporal variation in the hydrodynamic diameter of PLGA nanoparticles was observed in the presence of plasma proteins, which correlated with the amount of proteins adsorbed to each surface. Positively charged particles displayed the maximum size variation and protein adsorption. Cellular uptake of differentially charged nanoparticles was also concurrent with the quantity of adsorbed proteins, though there was no significant difference in their cytotoxicity. Haematological interactions (haemolysis and plasma coagulation times) of positively charged nanoparticles were considerably different from near-neutral and negative nanoparticles. Collectively, the results point to the interplay between plasma protein adsorption and cellular interactions of PLGA nanoparticles, which is governed by its surface charge, thereby necessitating a rational design of nanoparticles.
纳米颗粒与生物分子的初始相互作用对其毒性、功效、生物分布和清除有很大影响。本研究旨在了解聚合物纳米颗粒的表面电荷对其与血浆蛋白及细胞相互作用的影响。分别使用酪蛋白、聚乙烯醇和聚乙烯亚胺作为表面稳定剂制备了带负电荷、接近中性电荷和带正电荷的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒。在血浆蛋白存在的情况下，观察到PLGA纳米颗粒的流体动力学直径存在显著的时间变化，这与吸附到每个表面的蛋白量相关。带正电荷的颗粒表现出最大的尺寸变化和蛋白吸附。不同电荷纳米颗粒的细胞摄取也与吸附蛋白的量一致，尽管它们的细胞毒性没有显著差异。带正电荷的纳米颗粒的血液学相互作用（溶血和血浆凝固时间）与接近中性和带负电荷的纳米颗粒有很大不同。总体而言，结果表明PLGA纳米颗粒的血浆蛋白吸附和细胞相互作用之间存在相互影响，这由其表面电荷决定，因此需要对纳米颗粒进行合理设计。
