Nano Biomedical Research Center, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, P. R. China.
J Mater Chem B. 2019 Mar 28;7(12):2081-2091. doi: 10.1039/c9tb00002j. Epub 2019 Feb 25.
Clinically acceptable safety and efficacy are the most important issues for the design and synthesis of iron oxide MRI contrast agents. In order to meet the practical requirements, a kind of low molecular weight PAA-coated FeO nanoparticle (CS015) with super colloidal stability and low hypersensitivity benefitting from an ultrahigh carboxyl group density was developed in this study. The composition and physicochemical properties of the particles were characterized by TEM, XRD, FTIR and TGA. The ultrahigh density of COOH on the particles (33 COOH per nm) was verified while a core size of 5.1 nm and a dynamic diameter of 41 nm with a narrow distribution were also achieved. The particles still showed excellent dispersity and stability even after a spray-drying or freeze-drying process, exposure to high temperature sterilized conditions and long-term storage. The nanoparticles could quickly capture iron ions in bulk solution which was confirmed by ITC results, and the bioactive iron concentration of CS015 was greatly decreased (0.54 ± 0.05 mg L) compared to that of commercially available ferumoxytol, iron sucrose and VSOP. Free iron ion release was 1120 times lower than the toxic concentration of iron. An excellent biocompatibility of CS015 with no obvious cytotoxicity and low risk of hypersensitivity has been manifested by cytotoxicity experiments and a passive cutaneous anaphylaxis test. The T and T-weighted MRI contrast effects both in vitro and in vivo have also been verified which made CS015 a potential dual MRI contrast agent. Furthermore, theoretically calculated conformation was speculated and all the advantages mentioned above were benefited from the three dimensional brush-like texture of CS015. Therefore, these merits make the CS015 nanoplatform highly suitable in diagnostic applications as a MRI contrast agent.
临床可接受的安全性和有效性是设计和合成氧化铁磁共振成像对比剂的最重要问题。为了满足实际需求，本研究开发了一种具有超胶体稳定性和低超敏性的低分子量 PAA 包覆的 FeO 纳米颗粒（CS015），得益于超高的羧基密度。通过 TEM、XRD、FTIR 和 TGA 对颗粒的组成和理化性质进行了表征。验证了颗粒上超高密度的 COOH（每纳米 33 个 COOH），同时还实现了 5.1nm 的核尺寸和 41nm 的动态直径，分布较窄。即使经过喷雾干燥或冷冻干燥过程、暴露于高温灭菌条件和长期储存，颗粒仍表现出优异的分散性和稳定性。通过 ITC 结果证实，纳米颗粒能够迅速在体相溶液中捕获铁离子，并且 CS015 的生物活性铁浓度（0.54±0.05mg/L）与市售的 Ferumoxytol、蔗糖铁和 VSOP 相比大大降低。游离铁离子释放量比铁的毒性浓度低 1120 倍。通过细胞毒性实验和被动皮肤过敏反应试验，CS015 表现出良好的生物相容性，无明显细胞毒性和低超敏风险。体外和体内的 T 和 T1 加权磁共振成像对比效果也得到了验证，这使 CS015 成为一种潜在的双重磁共振成像对比剂。此外，还推测了理论计算的构象，CS015 的所有优点都得益于其三维刷状结构。因此，CS015 纳米平台作为磁共振成像对比剂在诊断应用中具有很高的适用性。
