Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, 1023 Shatai South Road, Guangzhou, 510515, Guangdong, China.
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Southern Medical University, 1023 Shatai South Road, Guangzhou, 510515, Guangdong, China.
J Nanobiotechnology. 2022 Jul 30;20(1):350. doi: 10.1186/s12951-022-01562-y.
Magnetic resonance imaging (MRI) has been widely using in clinical diagnosis, and contrast agents (CAs) can improve the sensitivity MRI. To overcome the problems of commercial Gd chelates-based T CAs, commercial magnetic iron oxide nanoparticles (MIONs)-based T CAs, and reported exceedingly small MIONs (ES-MIONs)-based T CAs, in this study, a facile co-precipitation method was developed to synthesize biodegradable and biocompatible ES-MIONs with excellent water-dispersibility using poly (aspartic acid) (PASP) as a stabilizer for T-weighted MRI of tumors. After optimization of the synthesis conditions, the final obtained ES-MION9 with 3.7 nm of diameter has a high r value (7.0 ± 0.4 mM s) and a low r/r ratio (4.9 ± 0.6) at 3.0 T. The ES-MION9 has excellent water dispersibility because of the excessive -COOH from the stabilizer PASP. The pharmacokinetics and biodistribution of ES-MION9 in vivo demonstrate the better tumor targetability and MRI time window of ES-MION9 than commercial Gd chelates. T-weighted MR images of aqueous solutions, cells and tumor-bearing mice at 3.0 T or 7.0 T demonstrate that our ES-MION9 has a stronger capability of enhancing the MRI contrast comparing with the commercial Gd chelates. The MTT assay, live/dead staining of cells, and H&E-staining indicate the non-toxicity and biosafety of our ES-MION9. Consequently, the biodegradable and biocompatible ES-MION9 with excellent water-dispersibility is an ideal T-weighted CAs with promising translational possibility to compete with the commercial Gd chelates.
磁共振成像（MRI）在临床诊断中得到了广泛应用，而对比剂（CAs）可以提高 MRI 的灵敏度。为了克服商业 Gd 螯合物基 T CAs、商业磁性氧化铁纳米粒子（MIONs）基 T CAs 以及报道的超小 MIONs（ES-MIONs）基 T CAs 的问题，本研究采用聚（天冬氨酸）（PASP）作为稳定剂，通过简便的共沉淀法合成了具有良好水溶性的可生物降解和生物相容性的 ES-MIONs，用于肿瘤的 T 加权 MRI。在优化了合成条件后，最终得到的 ES-MION9 粒径为 3.7nm，具有较高的 r 值（7.0±0.4 mM·s）和 r/r 比（4.9±0.6），在 3.0T 下。由于稳定剂 PASP 中过多的 -COOH，ES-MION9 具有优异的水分散性。ES-MION9 的体内药代动力学和生物分布表明，与商业 Gd 螯合物相比，ES-MION9 具有更好的肿瘤靶向性和 MRI 时间窗口。在 3.0T 或 7.0T 下，对水溶液、细胞和荷瘤小鼠的 T 加权 MR 图像表明，与商业 Gd 螯合物相比，我们的 ES-MION9 具有更强的增强 MRI 对比能力。MTT 试验、细胞死活染色和 H&E 染色表明，我们的 ES-MION9 具有非毒性和生物安全性。因此，具有良好水溶性的可生物降解和生物相容性的 ES-MION9 是一种理想的 T 加权 CAs，具有与商业 Gd 螯合物竞争的有前途的转化潜力。
