Gómez-González Elisabet, Caro Carlos, García-Martín María L, Becerro Ana Isabel, Ocaña Manuel
Instituto de Ciencia de Materiales de Sevilla (ICMS) CSIC-Universidad de Sevilla, c/Américo Vespucio, 49, 41092 Seville, Spain.
Instituto de Investigación Biomédica de Málaga - Plataforma Bionand (IBIMA-Plataforma BIONAND) and CIBER-BBN, Málaga 29590, Spain.
Nanoscale. 2022 Aug 11;14(31):11461-11470. doi: 10.1039/d2nr02630a.
The use of high-field magnets for magnetic resonance imaging (MRI) is expected to experience the fastest growth rate during the present decade. Although several CAs for MRI scanners using high magnetic fields have been reported, they are mostly based on fluoride matrices, which are known for their low chemical stability in aqueous suspensions. Chemically stable MRI CAs for high-field magnets are therefore needed to enable the advances in MRI technique. Herein, we synthesized uniform DyPO nanoparticles (NPs) with tuneable sizes between 23 and 57 nm using homogeneous precipitation in butanol. The NPs were successfully functionalized with polyacrylic acid (PAA) and showed good colloidal stability in aqueous suspensions. Chemical stability was also assessed in PBS, showing negligible solubility. The effect of particle size on the transversal relaxivity value () was further explored at 9.4 T, finding a clear increase in with particle size. The value found for the largest NPs was 516 mM s, which is, to the best of our knowledge, the highest value ever reported at 9.4 T for any Dy-based nanometric particles in the literature. Finally, the latter NPs were submitted to biosafety studies after polyethylene glycol (PEG) functionalization. Cell morphology, induction of necrotic/late apoptotic cells, and mitochondrial activity were thoroughly analyzed. The results clearly indicated negligible toxicity effects under the assayed conditions. Short- and long-term pharmacokinetics of the intravenously injected NPs were assessed by dynamic -weighted MRI and quantitative mapping, revealing faster liver than spleen uptake, while no accumulation was observed in the kidneys. Finally, no histopathological changes were observed in any of the studied organs, including the liver, kidney, spleen, and lung, which provide further evidence of the biocompatibility of DyPO NPs and, therefore, their suitability as bioimaging probes.
预计在本十年中,用于磁共振成像(MRI)的高场磁体的使用将经历最快的增长率。尽管已经报道了几种用于高磁场MRI扫描仪的造影剂(CAs),但它们大多基于氟化物基质,而氟化物基质在水性悬浮液中的化学稳定性较低是众所周知的。因此,需要化学稳定的高场磁体MRI造影剂来推动MRI技术的进步。在此,我们使用丁醇中的均匀沉淀法合成了尺寸在23至57nm之间可调的均匀DyPO纳米颗粒(NPs)。这些纳米颗粒成功地用聚丙烯酸(PAA)进行了功能化,并且在水性悬浮液中表现出良好的胶体稳定性。还在磷酸盐缓冲盐水(PBS)中评估了化学稳定性,显示溶解度可忽略不计。在9.4T下进一步探索了粒径对横向弛豫率值()的影响,发现随着粒径的增加而明显增加。对于最大的纳米颗粒所测得的值为516 mM s,据我们所知,这是文献中报道的在9.4T下任何基于Dy的纳米颗粒的最高值。最后,在聚乙二醇(PEG)功能化后,对后一种纳米颗粒进行了生物安全性研究。对细胞形态、坏死/晚期凋亡细胞的诱导以及线粒体活性进行了全面分析。结果清楚地表明在测定条件下毒性作用可忽略不计。通过动态加权MRI和定量成像评估静脉注射纳米颗粒的短期和长期药代动力学,发现肝脏摄取比脾脏快,而在肾脏中未观察到积累。最后,在包括肝脏、肾脏、脾脏和肺在内的任何研究器官中均未观察到组织病理学变化,这进一步证明了DyPO纳米颗粒的生物相容性,因此也证明了它们作为生物成像探针的适用性。