Department of Pharmacological and Pharmaceutical Sciences , College of Pharmacy, University of Houston , Houston , Texas 77024 , United States.
Department of Cancer Systems Imaging , The University of Texas MD Anderson Cancer Center , Houston , Texas 77054-1907 , United States.
Bioconjug Chem. 2018 Dec 19;29(12):4062-4071. doi: 10.1021/acs.bioconjchem.8b00690. Epub 2018 Nov 15.
Copper sulfide (CuS) nanoparticles have been considered one of the most clinical relevant nanosystems because of their straightforward chemistry, small particle size, low toxicity, and intrinsic theranostic characteristics. In our previous studies, radioactive [Cu]CuS nanoparticles were successfully developed to be used as efficient radiotracers for positron emission tomography and for photothermal ablation therapy of cancer cells using near-infrared laser irradiation. However, the major challenge of CuS nanoparticles as a theranostic platform is the lack of a means for effective targeted delivery to the tumor site. To overcome this challenge, we designed and synthesized angiogenesis-targeting [Cu]CuS nanoparticles, which are coupled with cyclic RGDfK peptide [c(RGDfK)] through polyethylene glycol (PEG) linkers using click chemistry. In assessing their tumor-targeting efficacy, we found that the tumor uptakes of [Cu]CuS-PEG-c(RGDfK) nanoparticles at 24 h after intravenous injection were significantly greater (8.6% ± 1.4% injected dose/gram of tissue) than those of nontargeted [Cu]CuS-PEG nanoparticles (4.3% ± 1.2% injected dose/gram of tissue, p < 0.05). Irradiation of tumors in mice administered [Cu]CuS-PEG-c(RGDfK) nanoparticles induced 98.7% necrotic areas. In contrast, irradiation of tumors in mice administered nontargeted CuS-PEG nanoparticles induced 59% necrotic areas ( p < 0.05). The angiogenesis-targeting [Cu]CuS nanoparticles may serve as a promising platform for image-guided ablation therapy with high efficacy and minimal side effects in future clinical translation of this novel class of multifunctional nanomaterials.
硫化铜 (CuS) 纳米粒子因其简单的化学性质、小粒径、低毒性和固有治疗诊断特性，被认为是最具临床相关性的纳米系统之一。在我们之前的研究中，成功开发了放射性 [Cu]CuS 纳米粒子，可作为正电子发射断层扫描的高效放射性示踪剂，并在近红外激光照射下用于癌细胞的光热消融治疗。然而，CuS 纳米粒子作为治疗诊断平台的主要挑战是缺乏有效靶向递送到肿瘤部位的手段。为了克服这一挑战，我们设计并合成了血管生成靶向 [Cu]CuS 纳米粒子，该纳米粒子通过点击化学用聚乙二醇 (PEG) 接头与环肽 RGDfK [c(RGDfK)] 偶联。在评估其肿瘤靶向功效时，我们发现静脉注射后 24 小时，[Cu]CuS-PEG-c(RGDfK) 纳米粒子的肿瘤摄取量明显更高（8.6%±1.4%注射剂量/克组织）比未靶向的 [Cu]CuS-PEG 纳米粒子（4.3%±1.2%注射剂量/克组织，p<0.05）。辐照给予 [Cu]CuS-PEG-c(RGDfK) 纳米粒子的小鼠肿瘤诱导了 98.7%的坏死区。相比之下，辐照给予未靶向 CuS-PEG 纳米粒子的小鼠肿瘤诱导了 59%的坏死区（p<0.05）。这种血管生成靶向 [Cu]CuS 纳米粒子可能成为一种有前途的平台，用于在未来的临床转化中进行高效、副作用最小的图像引导消融治疗。
