Semkina A, Abakumov M, Grinenko N, Abakumov A, Skorikov A, Mironova E, Davydova G, Majouga A G, Nukolova N, Kabanov A, Chekhonin V
Pirogov Russian National Research Medical University, Ostrovitianov 1, 117997 Moscow, Russia.
Pirogov Russian National Research Medical University, Ostrovitianov 1, 117997 Moscow, Russia; Lomonosov Moscow State University, Lenin Hills 1, 119991 Moscow, Russia.
Colloids Surf B Biointerfaces. 2015 Dec 1;136:1073-80. doi: 10.1016/j.colsurfb.2015.11.009. Epub 2015 Nov 10.
Superparamagnetic iron oxide magnetic nanoparticles (MNPs) are successfully used as contrast agents in magnetic-resonance imaging. They can be easily functionalized for drug delivery functions, demonstrating great potential for both imaging and therapeutic applications. Here we developed new pH-responsive theranostic core-shell-corona nanoparticles consisting of superparamagentic Fe3O4 core that displays high T2 relaxivity, bovine serum albumin (BSA) shell that binds anticancer drug, doxorubicin (Dox) and poly(ethylene glycol) (PEG) corona that increases stability and biocompatibility. The nanoparticles were produced by adsorption of the BSA shell onto the Fe3O4 core followed by crosslinking of the protein layer and subsequent grafting of the PEG corona using monoamino-terminated PEG via carbodiimide chemistry. The hydrodynamic diameter, zeta-potential, composition and T2 relaxivity of the resulting nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, thermogravimetric analysis and T2-relaxometry. Nanoparticles were shown to absorb Dox molecules, possibly through a combination of electrostatic and hydrophobic interactions. The loading capacity (LC) of the nanoparticles was 8 wt.%. The Dox loaded nanoparticles release the drug at a higher rate at pH 5.5 compared to pH 7.4 and display similar cytotoxicity against C6 and HEK293 cells as the free Dox.
超顺磁性氧化铁磁性纳米颗粒（MNPs）已成功用作磁共振成像中的造影剂。它们可以很容易地进行功能化以实现药物递送功能，在成像和治疗应用方面都显示出巨大潜力。在此，我们开发了新型的pH响应型诊疗用核壳冠层纳米颗粒，其由显示高T2弛豫率的超顺磁性Fe3O4核、结合抗癌药物阿霉素（Dox）的牛血清白蛋白（BSA）壳以及增加稳定性和生物相容性的聚乙二醇（PEG）冠层组成。纳米颗粒是通过将BSA壳吸附到Fe3O4核上，随后交联蛋白质层，并使用单氨基封端的PEG通过碳二亚胺化学方法接枝PEG冠层而制备的。使用透射电子显微镜、动态光散射、热重分析和T2弛豫测量对所得纳米颗粒的流体动力学直径、zeta电位、组成和T2弛豫率进行了表征。结果表明，纳米颗粒可能通过静电和疏水相互作用的组合吸收Dox分子。纳米颗粒的负载量（LC）为8 wt.%。与pH 7.4相比，负载Dox的纳米颗粒在pH 5.5时以更高的速率释放药物，并且对C6和HEK293细胞显示出与游离Dox相似的细胞毒性。
