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载多柔比星的不同功能化氧化铁纳米粒子的研究:对控制药物释放应用的启示。

Study on Doxorubicin Loading on Differently Functionalized Iron Oxide Nanoparticles: Implications for Controlled Drug-Delivery Application.

机构信息

Chemistry Department, Lomonosov Moscow State University, Lenin Hills, 119991 Moscow, Russia.

State Scientific Center of the Russian Federation, Joint Stock Company "State Order of the Red Banner of Labor Research Institute of Chemistry and Technology of Organoelement Compounds", 105118 Moscow, Russia.

出版信息

Int J Mol Sci. 2023 Feb 24;24(5):4480. doi: 10.3390/ijms24054480.

Abstract

Nanoplatforms applied for the loading of anticancer drugs is a cutting-edge approach for drug delivery to tumors and reduction of toxic effects on healthy cells. In this study, we describe the synthesis and compare the sorption properties of four types of potential doxorubicin-carriers, in which iron oxide nanoparticles (IONs) are functionalized with cationic (polyethylenimine, PEI), anionic (polystyrenesulfonate, PSS), and nonionic (dextran) polymers, as well as with porous carbon. The IONs are thoroughly characterized by X-ray diffraction, IR spectroscopy, high resolution TEM (HRTEM), SEM, magnetic susceptibility, and the zeta-potential measurements in the pH range of 3-10. The degree of doxorubicin loading at pH 7.4, as well as the degree of desorption at pH 5.0, distinctive to cancerous tumor environment, are measured. Particles modified with PEI were shown to exhibit the highest loading capacity, while the greatest release at pH 5 (up to 30%) occurs from the surface of magnetite decorated with PSS. Such a slow release of the drug would imply a prolonged tumor-inhibiting action on the affected tissue or organ. Assessment of the toxicity (using Neuro2A cell line) for PEI- and PSS-modified IONs showed no negative effect. In conclusion, the preliminary evaluation of the effects of IONs coated with PSS and PEI on the rate of blood clotting was carried out. The results obtained can be taken into account when developing new drug delivery platforms.

摘要

纳米平台被应用于负载抗癌药物,这是一种向肿瘤部位递药并降低对健康细胞毒性作用的前沿方法。在本研究中,我们描述了四种潜在阿霉素载体的合成,并对其进行了比较,这四种载体分别是用阳离子(聚乙烯亚胺,PEI)、阴离子(聚苯乙烯磺酸钠,PSS)和非离子(葡聚糖)聚合物以及多孔碳功能化的氧化铁纳米颗粒(IONs)。IONs 通过 X 射线衍射、红外光谱、高分辨率透射电镜(HRTEM)、扫描电子显微镜、磁化率和在 3-10 pH 范围内的zeta 电位测量进行了全面表征。在 pH 7.4 下测量了载药程度,以及在 pH 5.0 下解吸程度,这与癌肿瘤环境具有独特性。结果表明,用 PEI 修饰的粒子表现出最高的载药能力,而在 pH 5 下(高达 30%)从用 PSS 修饰的磁铁矿表面释放出的药物最多。这种药物的缓慢释放将意味着对受影响的组织或器官的肿瘤抑制作用延长。用神经 2A 细胞系对 PEI 和 PSS 修饰的 IONs 的毒性(使用神经 2A 细胞系)进行评估,结果表明没有负面影响。总之,对用 PSS 和 PEI 涂层的 IONs 对凝血速度的影响进行了初步评估。在开发新的药物传递平台时,可以考虑获得的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a23a/10002596/91ba0116861d/ijms-24-04480-g001.jpg

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