Istrate Claudia Mihaela, Holban Alina Maria, Grumezescu Alexandru Mihai, Mogoantă Laurenţiu, Mogoşanu George Dan, Savopol Tudor, Moisescu Mihaela, Iordache Minodora, Vasile Bogdan Stefan, Kovacs Eugenia
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Romania;
Rom J Morphol Embryol. 2014;55(3):849-56.
The interaction of nanomaterials with cells and lipid bilayers is critical in many applications such as phototherapy, imaging and drug/gene delivery. These applications require a firm control over nanoparticle-cell interactions, which are mainly dictated by surface properties of the nanoparticles. The aim of this study was to investigate the interaction of Fe3O4 nanoparticles functionalized with several wide use antibiotics with opossum kidney (OK) cellular membranes in order to reveal changes in the membrane organization at different temperatures. We also investigated the in vivo biodistribution of the tested nanoparticles in a mouse model. Our results showed that, at low temperatures (31-35°C), plain Fe3O4 nanoparticles induced a drop of the membrane fluidity, while at physiological or higher temperatures (37-39°C) the membrane fluidity was increased. On the other hand, when nanoparticles functionalized with the tested antibiotics were used, we observed that the effect was opposite as compared to control Fe3O4 nanoparticles. Although most of antibiotics, used as plain solutions or linked on magnetite nanoparticles, proved heterogeneous effect on in vitro OK cells membrane fluidity, the aminoglycosides streptomycin and neomycin, used both as plain solutions and also combined with nanoparticles kept the same effect in all experimental conditions, increasing the membrane fluidity of OK cells plasma membrane. In vivo results showed that the antibiotic functionalized nanoparticles have a similar biodistribution pattern within the mouse body, being transported through the blood flow and entering the macrophages through endocytosis. Functionalized magnetite nanoparticles manifested a preferential biodistribution pattern, clustering within the lungs and spleen of treated mice. These results demonstrate that antibiotics manifest a different effect on plasma membrane fluidity depending on their type and temperature. Magnetite nanoparticles may interfere with antibiotic-cellular interactions by changing the plasma membrane fluidity. The fact that the antibiotic functionalized magnetite nanoparticles have a similar biodistribution pattern, are transported through the blood flow, and they increase the cellular uptake of the drug, suggest that they may be used for further studies aiming to develop personalized targeted delivery and controlled release nanoshuttles for treating localized and systemic infections.
纳米材料与细胞及脂质双层的相互作用在光疗、成像以及药物/基因递送等诸多应用中至关重要。这些应用需要对纳米颗粒与细胞的相互作用进行严格控制，而这种相互作用主要由纳米颗粒的表面性质决定。本研究的目的是探究用几种广泛使用的抗生素功能化的Fe3O4纳米颗粒与负鼠肾（OK）细胞膜的相互作用，以揭示不同温度下膜组织的变化。我们还研究了受试纳米颗粒在小鼠模型中的体内生物分布。我们的结果表明，在低温（31 - 35°C）下，普通的Fe3O4纳米颗粒会导致膜流动性下降，而在生理温度或更高温度（37 - 39°C）下，膜流动性会增加。另一方面，当使用用受试抗生素功能化的纳米颗粒时，我们观察到与对照Fe3O4纳米颗粒相比，效果相反。尽管大多数用作普通溶液或连接在磁铁矿纳米颗粒上的抗生素对体外OK细胞膜流动性表现出异质性影响，但氨基糖苷类的链霉素和新霉素，无论是用作普通溶液还是与纳米颗粒结合，在所有实验条件下都保持相同的效果，增加了OK细胞质膜的流动性。体内结果表明，抗生素功能化的纳米颗粒在小鼠体内具有相似的生物分布模式，通过血流运输并通过内吞作用进入巨噬细胞。功能化的磁铁矿纳米颗粒表现出优先的生物分布模式，聚集在受试小鼠的肺和脾中。这些结果表明，抗生素根据其类型和温度对质膜流动性表现出不同的影响。磁铁矿纳米颗粒可能通过改变质膜流动性来干扰抗生素与细胞的相互作用。抗生素功能化的磁铁矿纳米颗粒具有相似的生物分布模式、通过血流运输且增加药物的细胞摄取这一事实表明，它们可用于进一步研究，旨在开发用于治疗局部和全身感染的个性化靶向递送和控释纳米载体
