State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Center for Molecular Imaging, Department of Radiology, University of Michigan, Michigan 48109-2200, USA.
Acta Biomater. 2017 Oct 1;61:193-203. doi: 10.1016/j.actbio.2017.08.011. Epub 2017 Aug 8.
Various carbonaceous nanomaterials, including fullerene, carbon nanotube, graphene, and carbon dots, have attracted increasing attention during past decades for their potential applications in biological imaging and therapy. In this study, we have developed a fullerene-based tumor-targeted positron emission tomography (PET) imaging probe. Water-soluble functionalized C conjugates were radio-labeled with Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for targeting of integrin αβ in glioblastoma. The specificity of fluorescein-labeled C conjugates against cellular integrin αβ was evaluated in U87MG (integrin αβ positive) and MCF-7 cells (integrin αβ negative) by confocal fluorescence microscopy and flow cytometry. Our results indicated that cRGD-conjugated C derivatives showed better cellular internalization compared with C derivatives without the cRGD attachment. Moreover, an interesting finding on intra-nuclei transportation of cRGD-conjugated C derivatives was observed in U87MG cells. In vivo serial PET studies showed preferential accumulation of cRGD-conjugated C derivatives at in U87MG tumors. In addition, the pharmacokinetic profiles of these fullerene-based nanoparticles conjugated with cRGD and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) fit well with the three compartment model. The renal clearance of C-based nanoparticles is remarkably fast, which makes this material very promising for safer cancer theranostic applications.
Safety is one of the major concerns for nanomedicine and nanomaterials with fast clearance profile are highly desirable. Fullerene is a distinct type of zero-dimensional carbon nanomaterial with ultrasmall size, uniform dispersity, and versatile reactivity. Here we have developed a fullerene-based tumor-targeted positron emission tomography imaging probe using water-soluble functionalized C conjugates radio-labeled with Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for glioblastoma targeting. The improved tumor targeting property along with fast renal clearance behavior of C-based nanoparticles makes this material very promising for future safer cancer theranostic applications.
在过去几十年中，各种碳纳米材料，包括富勒烯、碳纳米管、石墨烯和碳点，由于它们在生物成像和治疗方面的潜在应用而引起了越来越多的关注。在这项研究中，我们开发了一种基于富勒烯的肿瘤靶向正电子发射断层扫描（PET）成像探针。水溶性功能化 C 缀合物用 Cu 放射性标记，并与环（精氨酸-甘氨酸-天冬氨酸）肽（cRGD）修饰，以靶向神经胶质瘤中的整合素 αβ。通过共聚焦荧光显微镜和流式细胞术评估荧光标记的 C 缀合物对 U87MG（整合素 αβ 阳性）和 MCF-7 细胞（整合素 αβ 阴性）中细胞整合素 αβ 的特异性。结果表明，与没有 cRGD 附着的 C 衍生物相比，cRGD 缀合的 C 衍生物显示出更好的细胞内化。此外，在 U87MG 细胞中观察到 cRGD 缀合的 C 衍生物在细胞核内的有趣运输。体内连续 PET 研究表明，cRGD 缀合的 C 衍生物在 U87MG 肿瘤中的优先积累。此外，这些与 1,4,7-三氮杂环壬烷-1,4,7-三乙酸（NOTA）缀合的富勒烯纳米粒子的药代动力学特征与三房室模型拟合良好。基于 C 的纳米粒子的肾清除率非常快，这使得该材料非常有希望用于更安全的癌症治疗应用。
安全性是纳米医学的主要关注点之一，具有快速清除谱的纳米材料是非常理想的。富勒烯是一种独特的零维碳纳米材料，具有超小尺寸、均匀分散性和多功能反应性。在这里，我们使用 Cu 放射性标记的水溶性功能化 C 缀合物和环（精氨酸-甘氨酸-天冬氨酸）肽（cRGD）修饰，开发了一种基于富勒烯的肿瘤靶向正电子发射断层扫描成像探针，用于神经胶质瘤靶向。基于 C 的纳米粒子的肿瘤靶向性提高和快速的肾脏清除行为使该材料非常有希望用于未来更安全的癌症治疗应用。
