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用于磁共振成像诊断中增强造影的具有自组装聚丙烯酸酯-聚乙二醇刷的超顺磁性氧化铁纳米颗粒的聚乙二醇化

PEGylation of Superparamagnetic Iron Oxide Nanoparticles with Self-Organizing Polyacrylate-PEG Brushes for Contrast Enhancement in MRI Diagnosis.

作者信息

Illés Erzsébet, Szekeres Márta, Tóth Ildikó Y, Farkas Katalin, Földesi Imre, Szabó Ákos, Iván Béla, Tombácz Etelka

机构信息

Department of Physical Chemistry and Materials Science, University of Szeged, Aradi Vt. 1, H-6720 Szeged, Hungary.

Department of Laboratory Medicine, University of Szeged, Semmelweis u. 6, H-6720 Szeged, Hungary.

出版信息

Nanomaterials (Basel). 2018 Sep 29;8(10):776. doi: 10.3390/nano8100776.

DOI:10.3390/nano8100776
PMID:30274317
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6215243/
Abstract

For biomedical applications, superparamagnetic nanoparticles (MNPs) have to be coated with a stealth layer that provides colloidal stability in biological media, long enough persistence and circulation times for reaching the expected medical aims, and anchor sites for further attachment of bioactive agents. One of such stealth molecules designed and synthesized by us, poly(polyethylene glycol methacrylate--acrylic acid) referred to as P(PEGMA-AA), was demonstrated to make MNPs reasonably resistant to cell internalization, and be an excellent candidate for magnetic hyperthermia treatments in addition to possessing the necessary colloidal stability under physiological conditions (Illés et al. J. Magn. Magn. Mater. 2018, 451, 710⁻720). In the present work, we elaborated on the molecular background of the formation of the P(PEGMA-AA)-coated MNPs, and of their remarkable colloidal stability and salt tolerance by using potentiometric acid⁻base titration, adsorption isotherm determination, infrared spectroscopy (FT-IR ATR), dynamic light scattering, and electrokinetic potential determination methods. The P(PEGMA-AA)@MNPs have excellent blood compatibility as demonstrated in blood sedimentation, smears, and white blood cell viability experiments. In addition, blood serum proteins formed a protein corona, protecting the particles against aggregation (found in dynamic light scattering and electrokinetic potential measurements). Our novel particles also proved to be promising candidates for MRI diagnosis, exhibiting one of the highest values of 2 relaxivity (451 mMs) found in literature.

摘要

对于生物医学应用而言，超顺磁性纳米颗粒（MNPs）必须包覆一层隐身层，该隐身层要能在生物介质中提供胶体稳定性，具有足够长的持续时间和循环时间以实现预期的医学目标，还要有用于进一步连接生物活性剂的锚定位点。我们设计并合成的一种这样的隐身分子，聚（聚乙二醇甲基丙烯酸酯 - 丙烯酸），简称为P（PEGMA - AA），已被证明能使MNPs对细胞内化具有合理的抗性，并且除了在生理条件下具有必要的胶体稳定性外，还是磁热疗治疗的优秀候选物（Illés等人，《J. Magn. Magn. Mater.》2018年，451卷，710 - 720页）。在本工作中，我们通过电位酸碱滴定、吸附等温线测定、红外光谱（傅里叶变换红外衰减全反射光谱，FT - IR ATR）、动态光散射和电动电位测定方法，阐述了P（PEGMA - AA）包覆的MNPs形成的分子背景及其显著的胶体稳定性和耐盐性。如血沉、涂片和白细胞活力实验所示，P（PEGMA - AA）@MNPs具有优异的血液相容性。此外，血清蛋白形成了蛋白质冠层，保护颗粒不发生聚集（在动态光散射和电动电位测量中发现）。我们的新型颗粒也被证明是MRI诊断的有前景的候选物，展现出文献中报道的最高横向弛豫率值之一（451 mM⁻¹s⁻¹）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/62b9d75a20bb/nanomaterials-08-00776-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/55bf4647e9ab/nanomaterials-08-00776-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/b744fef9aa12/nanomaterials-08-00776-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/89c17f4e4874/nanomaterials-08-00776-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/2d2a7157df83/nanomaterials-08-00776-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/113cff018041/nanomaterials-08-00776-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/f35bbba242fc/nanomaterials-08-00776-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/a0cd0901429a/nanomaterials-08-00776-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/862a794d1725/nanomaterials-08-00776-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/4eb48ea921d5/nanomaterials-08-00776-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/ce1dd25d3ee4/nanomaterials-08-00776-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/d2c357fbcfb9/nanomaterials-08-00776-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/62b9d75a20bb/nanomaterials-08-00776-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/55bf4647e9ab/nanomaterials-08-00776-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/b744fef9aa12/nanomaterials-08-00776-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/89c17f4e4874/nanomaterials-08-00776-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/2d2a7157df83/nanomaterials-08-00776-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/113cff018041/nanomaterials-08-00776-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/f35bbba242fc/nanomaterials-08-00776-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/a0cd0901429a/nanomaterials-08-00776-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/862a794d1725/nanomaterials-08-00776-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/4eb48ea921d5/nanomaterials-08-00776-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/ce1dd25d3ee4/nanomaterials-08-00776-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/d2c357fbcfb9/nanomaterials-08-00776-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed61/6215243/62b9d75a20bb/nanomaterials-08-00776-g012.jpg

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