MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, China.
ACS Appl Mater Interfaces. 2014 Apr 23;6(8):5657-68. doi: 10.1021/am5001823. Epub 2014 Apr 10.
Gold nanorods (AuNRs), because of their strong absorption of near-infrared (NIR) light, are very suitable for in vivo photothermal therapy of cancer. However, appropriate surface modification must be performed on AuNRs before their in vivo application because of the high toxicity of their original stabilizer cetyltrimethylammonium bromide. Multidentate ligands have attracted a lot of attention for modification of inorganic nanoparticles (NPs) because of their high ligand affinity and multifunctionality, while the therapeutic effect of multidentate ligands modified NPs in vivo remains unexplored. Here, we modified AuNRs with a polythiol PEG-based copolymer. The multidentate PEG coated AuNRs (AuNR-PTPEGm950) showed good stabilities in high saline condition and wide pH range. And they had much stronger resistance to ligand competition of dithiothreitol (DTT) than AuNRs coated by monothiol-anchored PEG. The AuNR-PTPEGm950 had very low cytotoxicity and showed high efficacy for the ablation of cancer cells in vitro. Moreover, the AuNR-PTPEGm950 showed good stability in serum, and they had a long circulation time in blood that led to a high accumulation in tumors after intravenous injection. In vivo photothermal therapy showed that tumors were completely cured without reoccurrence by one-time irradiation of NIR laser after a single injection of these multidentate PEG modified AuNRs.
金纳米棒(AuNRs)由于其对近红外(NIR)光的强吸收,非常适合用于癌症的体内光热治疗。然而,由于其原始稳定剂十六烷基三甲基溴化铵的高毒性,在 AuNRs 进行体内应用之前,必须对其进行适当的表面修饰。多齿配体因其高配体亲和力和多功能性而引起了人们对无机纳米粒子(NPs)修饰的极大关注,而多齿配体修饰的 NPs 在体内的治疗效果仍有待探索。在这里,我们用一种聚硫醇聚乙二醇基共聚物对 AuNRs 进行了修饰。多齿 PEG 修饰的 AuNRs(AuNR-PTPEGm950)在高盐条件和宽 pH 范围内表现出良好的稳定性。与由单硫醇锚定的 PEG 修饰的 AuNRs 相比,它们对二硫苏糖醇(DTT)的配体竞争具有更强的抵抗力。AuNR-PTPEGm950 的细胞毒性很低,在体外对癌细胞的消融具有很高的疗效。此外,AuNR-PTPEGm950 在血清中表现出良好的稳定性,并且在静脉注射后,它们在血液中的循环时间很长,导致在肿瘤中的高积累。体内光热治疗表明,通过单次注射这些多齿 PEG 修饰的 AuNRs 后,用近红外激光一次性照射,肿瘤完全治愈,无复发。