64Cu-Doped PdCu@Au Tripods: A Multifunctional Nanomaterial for Positron Emission Tomography and Image-Guided Photothermal Cancer Treatment
64Cu-Doped PdCu@Au Tripods: A Multifunctional Nanomaterial for Positron Emission Tomography and Image-Guided Photothermal Cancer Treatment
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DOI：
10.1021/acsnano.5b07968
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发表时间：
2016-03-01
期刊：
影响因子：
17.1
通讯作者：
Xia, Younan
中科院分区：
文献类型：
--
作者：
Pang, Bo;Zhao, Yongfeng;Xia, Younan
本文报道了通过直接将放射性Cu-64原子掺入晶格中，用于正电子发射断层扫描（PET）和图像引导光热癌症治疗的放射性标记的PdCu@Au核-壳三脚架的简易合成。除了良好控制的比活度和物理尺寸之外，该三脚架还具有由用作Au壳涂层模板的PdCu三脚架决定的独特形态。Au壳层为纳米结构提供了在近红外区域的强吸收，并有效地防止了核心中的Cu和Cu-64原子的氧化和溶解。当与D-Ala（1）-肽T-酰胺（DAPTA）缀合时，核壳三脚架在靶向C-C趋化因子受体5（CCRS）方面显示出极大的增强，C-C趋化因子受体5是一种新鉴定的在三阴性乳腺癌（TNBC）中上调的治疗诊断靶标。具体而言，在注射后24小时，在原位小鼠4 T1 TNBC模型中，相对于其非靶向对应物，臂长约45 nm的CCRS靶向三足动物分别显示肿瘤-血液和肿瘤-肌肉摄取比增加2倍和6倍。通过竞争性受体阻断研究进一步验证靶向特异性。我们还证明了使用这些靶向的放射性三脚架在PET成像指导下在4 T1肿瘤模型中进行有效的光热治疗。通过使用P-18-氟脱氧葡萄糖PET/CT成像显示的肿瘤代谢活性的显著降低证实了治疗的疗效。综上所述，我们相信Cu-64掺杂的PdCu@Au三脚架可以作为PET成像和图像引导光热癌症治疗的多功能平台。
This article reports a facile synthesis of radiolabeled PdCu@Au core-shell tripods for use in positron emission tomography (PET) and image-guided photothermal cancer treatment by directly incorporating radioactive Cu-64 atoms into the crystal lattice. The tripod had a unique morphology determined by the PdCu tripod that served as a template for the coating of Au shell, in addition to well-controlled specific activity and physical dimensions. The Au shell provided the nanostructure with strong absorption in the near-infrared region and effectively prevented the Cu and Cu-64 atoms in the, core from oxidization and dissolution. When conjugated with D-Ala(1)-peptide T-amide (DAPTA), the core shell tripods showed great enhancement in targeting the C-C chemokine receptor 5 (CCRS), a newly identified theranostic target up-regulated in triple negative breast cancer (TNBC). Specifically, the CCRS-targeted tripods with an arm length of about 45 nm showed 2- and 6-fold increase in tumor-to-blood and tumor-to-muscle uptake ratios, respectively, relative to their nontargeted counterpart in an orthotopic mouse 4T1 TNBC model at 24 h postinjection. The targeting specificity was further validated via a competitive receptor blocking study. We also demonstrated the use of these targeted, radioactive tripods for effective photothermal treatment in the 4T1 tumor model as guided by PET imaging. The efficacy of treatment was confirmed by the significant reduction in tumor metabolic activity revealed through the use of P-18-fluorodeoxyglucose PET/CT imaging. Taken together, we believe that the Cu-64-doped PdCu@Au tripods could serve as a multifunctional platform for both PET imaging and image-guided photothermal cancer therapy.