Yao Hanchun, Su Li, Zeng Man, Cao Li, Zhao Weiwei, Chen Chengqun, Du Bin, Zhou Jie
School of Pharmaceutical Sciences, Zhengzhou University; Collaborative Innovation Center of Drug Research and Safety Evaluation, Henan Province.
School of Pharmaceutical Sciences, Zhengzhou University.
Int J Nanomedicine. 2016 Sep 6;11:4423-4438. doi: 10.2147/IJN.S108039. eCollection 2016.
Carbon dots (CDs) are one of the most highlighted carbon-based materials for biological applications, such as optical imaging nanoprobes, which are used for labeling cells in cancer treatment mainly due to their biocompatibility and unique optical properties. In this study, gadolinium (Gd)-complex-containing CDs were obtained through a one-step microwave method to develop multimodal nanoprobes integrating the advantages of optical and magnetic imaging. The obtained Gd-CDs exhibited highly fluorescent properties with excellent water solubility and biological compatibility. Natural apoferritin (AFn) nanocages, an excellent drug delivery carrier, are hollow in structure, with their pH-dependent, unfolding-refolding process at pH 2.0 and 7.4. The chemotherapeutic drug doxorubicin (DOX) can be highly effective and encapsulated into AFn cavity. A widely used tumor-targeting molecule, folic acid (FA), functionalized the surface of AFn to obtain an active tumor targeting effect on MCF-7 cells and malignant tumors in mice models. In this study, an AFn nanocarrier encapsulating high concentration of DOX labeled with magnetic and fluorescent Gd-CDs probe was developed. Gd-CDs exhibited a unique green photoluminescence and almost no toxicity compared with free GdCl. Furthermore, Gd-doped CDs significantly increased the circulation time and decreased the toxicity of Gd in in vitro and in vivo magnetic resonance imaging, which demonstrated that the AFn nanocages labeled with Gd-CD compounds could serve as an excellent T contrast agent for magnetic resonance imaging. The self-assembling multifunctional Gd-CDs/AFn (DOX)/FA nanoparticles have a great potential for cancer theranostic applications.
碳点(CDs)是生物应用中最受关注的碳基材料之一,例如光学成像纳米探针,主要由于其生物相容性和独特的光学特性,被用于癌症治疗中的细胞标记。在本研究中,通过一步微波法获得了含钆(Gd)配合物的碳点,以开发整合光学和磁共振成像优势的多模态纳米探针。所获得的钆-碳点表现出高荧光特性,具有优异的水溶性和生物相容性。天然脱铁铁蛋白(AFn)纳米笼是一种出色的药物递送载体,结构中空,在pH 2.0和7.4时具有pH依赖性的解折叠-再折叠过程。化疗药物阿霉素(DOX)能高效地封装到AFn腔内。一种广泛使用的肿瘤靶向分子叶酸(FA)对AFn表面进行功能化,以对MCF-7细胞和小鼠模型中的恶性肿瘤产生主动肿瘤靶向作用。在本研究中,开发了一种包裹高浓度用磁性和荧光钆-碳点探针标记的DOX的AFn纳米载体。与游离的GdCl相比,钆-碳点表现出独特的绿色光致发光且几乎没有毒性。此外,钆掺杂的碳点在体外和体内磁共振成像中显著增加了循环时间并降低了钆的毒性,这表明用钆-碳点化合物标记的AFn纳米笼可作为磁共振成像的优良T1造影剂。自组装多功能钆-碳点/AFn(DOX)/FA纳米颗粒在癌症诊疗应用中具有巨大潜力。