Zhang Weijie, Zhang Zhongyue, Lou Shitong, Chang Zhiwei, Wen Baohong, Zhang Tao
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Pharmacol. 2022 Jul 15;13:918819. doi: 10.3389/fphar.2022.918819. eCollection 2022.
The use of iron oxide (FeO) nanoparticles as novel contrast agents for magnetic resonance imaging (MRI) has attracted great interest due to their high relaxivity. However, both poor colloidal stability and lack of effective targeting ability have impeded their further expansion in the clinics. Here, we reported the creation of hyaluronic acid (HA)-stabilized FeO nanoparticles prepared by a hydrothermal co-precipitation method and followed by electrostatic adsorption of HA onto the nanoparticle surface. The water-soluble HA functions not only as a stabilizer but also as a targeting ligand with high affinity for the CD44 receptor overexpressed in many tumors. The resulting HA-stabilized FeO nanoparticles have an estimated size of sub-20 nm as observed by transmission electron microscopy (TEM) imaging and exhibited long-term colloidal stability in aqueous solution. We found that the nanoparticles are hemocompatible and cytocompatible under certain concentrations. As verified by quantifying the cellular uptake, the FeO@HA nanoparticles were able to target a model cell line (HeLa cells) overexpressing the CD44 receptor through an active pathway. In addition, we showed that the nanoparticles can be used as effective contrast agents for MRI both in HeLa cells and in a xenografted HeLa tumor model in rodents. We believe that our findings shed important light on the use of active targeting ligands to improve the contrast of lesion for tumor-specific MRI in the nano-based diagnosis systems.
由于具有高弛豫率，氧化铁（FeO）纳米颗粒作为磁共振成像（MRI）的新型造影剂已引起了极大的关注。然而，较差的胶体稳定性和缺乏有效的靶向能力阻碍了它们在临床上的进一步推广。在此，我们报道了通过水热共沉淀法制备透明质酸（HA）稳定的FeO纳米颗粒，并随后通过静电吸附将HA吸附到纳米颗粒表面。水溶性HA不仅作为稳定剂，还作为对许多肿瘤中过表达的CD44受体具有高亲和力的靶向配体。通过透射电子显微镜（TEM）成像观察，所得的HA稳定的FeO纳米颗粒估计尺寸小于20nm，并且在水溶液中表现出长期的胶体稳定性。我们发现，在一定浓度下，纳米颗粒具有血液相容性和细胞相容性。通过量化细胞摄取验证，FeO@HA纳米颗粒能够通过主动途径靶向过表达CD44受体的模型细胞系（HeLa细胞）。此外，我们表明，纳米颗粒在HeLa细胞和啮齿动物的异种移植HeLa肿瘤模型中都可以用作MRI的有效造影剂。我们相信，我们的发现为在基于纳米的诊断系统中使用主动靶向配体改善肿瘤特异性MRI病变的对比度提供了重要启示。
