BIONAND, Andalusian Centre for Nanomedicine and Biotechnology, BIONAND (Junta de Andalucía-Universidad de Málaga), Parque Tecnológico de Andalucía, Málaga, Spain.
Nanoscale. 2015 Feb 7;7(5):2050-9. doi: 10.1039/c4nr05781c.
Magnetic resonance based molecular imaging has emerged as a very promising technique for early detection and treatment of a wide variety of diseases, including cancer, neurodegenerative disorders, and vascular diseases. The limited sensitivity and specificity of conventional MRI are being overcome by the development of a new generation of contrast agents, using nanotechnology approaches, with improved magnetic and biological properties. In particular, for molecular imaging, high specificity, high sensitivity, and long blood circulation times are required. Furthermore, the lack of toxicity and immunogenicity together with low-cost scalable production are also necessary to get them into the clinics. In this work, we describe a facile, robust and cost-effective ligand-exchange method to synthesize dual T1 and T2 MRI contrast agents with long circulation times. These contrast agents are based on manganese ferrite nanoparticles (MNPs) between 6 and 14 nm in size covered by a 3 kDa polyethylene glycol (PEG) shell that leads to a great stability in aqueous media with high crystallinity and magnetization values, thus retaining the magnetic properties of the uncovered MNPs. Moreover, the PEGylated MNPs have shown different relaxivities depending on their size and the magnetic field applied. Thus, the 6 nm PEGylated MNPs are characterized by a low r2/r1 ratio of 4.9 at 1.5 T, hence resulting in good dual T1 and T2 contrast agents under low magnetic fields, whereas the 14 nm MNPs behave as excellent T2 contrast agents under high magnetic fields (r2 = 335.6 mM(-1) s(-1)). The polymer core shell of the PEGylated MNPs minimizes their cytotoxicity, and allows long blood circulation times. This combination of cellular compatibility and excellent T2 and r2/r1 values under low magnetic fields, together with long circulation times, make these nanomaterials very promising contrast agents for molecular imaging.
基于磁共振的分子成像是一种很有前途的技术，可用于早期检测和治疗多种疾病，包括癌症、神经退行性疾病和血管疾病。通过使用纳米技术方法开发新一代对比剂，可以克服传统 MRI 的灵敏度和特异性有限的问题，这些对比剂具有改进的磁学和生物学特性。特别是对于分子成像，需要高特异性、高灵敏度和长血液循环时间。此外，还需要缺乏毒性和免疫原性以及低成本的可扩展生产，以便将其应用于临床。在这项工作中，我们描述了一种简便、稳健且具有成本效益的配体交换方法，用于合成具有长血液循环时间的双 T1 和 T2 MRI 对比剂。这些对比剂基于尺寸在 6 至 14nm 之间的锰铁氧体纳米颗粒 (MNPs)，表面覆盖有 3kDa 的聚乙二醇 (PEG) 壳，这导致其在高结晶度和磁化值的水性介质中具有很好的稳定性，从而保留了未覆盖的 MNPs 的磁性。此外，PEG 化 MNPs 的弛豫率取决于其尺寸和施加的磁场。因此，6nm PEG 化 MNPs 的 r2/r1 比在 1.5T 时为 4.9，因此在低磁场下表现出良好的双 T1 和 T2 对比剂特性，而 14nm MNPs 在高磁场下表现出良好的 T2 对比剂特性（r2=335.6mM-1s-1）。PEG 化 MNPs 的聚合物核壳可最大限度地降低其细胞毒性，并延长血液循环时间。这些纳米材料具有细胞相容性和在低磁场下的优异 T2 和 r2/r1 值以及长血液循环时间，因此非常有前途成为分子成像的对比剂。
