内生型转铁蛋白-金纳米簇探针的合成及其对前列腺癌的靶向成像研究  

Transferrin Functionalized Gold Nanoclusters as a Near-Infrared Fluorescence Turn-on Probe for Targeted Imaging of Prostate Cancer

作　　者：张恩龙[1] 张雪宁[1] 赵阳[1] 张骐[1] 彭景[1] 吴梦琳[1] 

机构地区：[1]天津医科大学第二医院放射科,300211

出　　处：《临床放射学杂志》2016年第6期956-960,共5页Journal of Clinical Radiology

摘　　要：目的以转铁蛋白(transferrin,Tf)为模板,氯金酸为原料,原位合成靶向荧光探针-内生型转铁蛋白-金纳米簇(gold nanoclusters,Au NCs),并以前列腺癌(prostate cancer,PCa)为模型,探讨该荧光探针的靶向成像效果。方法利用场发射透射电子显微镜及粒度分析仪分析所合成的荧光探针的形貌、水合粒径及分布;利用紫外-可见分光光度计及荧光分光光度计对其光学性能进行表征;MTT法检测细胞毒性;并通过细胞荧光成像及竞争抑制实验表征其肿瘤的特异性靶向效果;静脉注射Tf-Au NCs至PC-3种植瘤鼠体内,进行连续荧光成像,评价其肿瘤靶向成像效果;通过组织病理学明确其活体毒性。结果本研究制备的Tf-Au NCs粒径约为3 nm,荧光发射峰为700 nm,保留了Tf及金纳米簇的性能;细胞成像结果显示Tf-Au NCs对前列腺肿瘤细胞(PC-3)特异性靶向效果好;小动物活体成像结果显示Tf-Au NCs探针仅需15 min即可准确显示肿瘤部位,至2 h时肿瘤区荧光强度达峰值,表明其具有良好的活体肿瘤成像能力;病理学结果表明Tf-Au NCs具有良好的生物相容性。结论 Tf-Au NCs荧光探针具有良好的光学性能、特异靶向能力,并具有优异的荧光成像能力及良好的生物相容性,将有望应用于PCa的早期影像学分析。Objective To explore the effect of transferrin（Tf） functionalized gold nanoclusters（Au NCs） on the nearinfrared targeted imaging of prostate cancer in vivo.Methods Tf-AuNCs were synthesized by using Tf and hydrogen tetrachloroaurate（III） trihydrate（HAuCl4·3H2O）.The transmission electron microscopy（TEM） and dynamic light scattering were performed to detect the morphology,the mean hydrodynamic particle size and size distribution.Fluorescence absorption and emission spectra and UV-vis-NIR absorption spectra were obtained on spectrofluorometer and UV-Vis-NIR spectrophotometer,respectively.The cytotoxicity of the prepared probe was evaluated by MTT assay.In vitro imaging and the competition experiment with unconjugated Tf were used to assess the binding specialty of Tf-AuNCs.PC-3 cells were subcutaneously transplanted into the left shoulder of BALB/c nude mice to generate tumour-bearing animal models.Dynamic fluorescence imaging was carried out over sequential time points after vein injection of Tf-AuNCs.Finally,histological examination was used to investigate the potential toxicity to major organs.Results Tf-AuNCs were successfully synthesized using Tf as stabilizer.TEM revealed good size uniformity with an average size of less than 3 nm.The prepared TfAu NCs presented low cytotoxicity to cells and excellent optical properties,emitting strong NIR fluorescence with the maximum fluorescence emission at the wavelength of 700 nm.Meanwhile,Tf-AuNCs showed great tumour-targeting ability.With the analysis of the real-time fluorescence imaging,the obvious fluorescence could be observed in tumour region as early as 15 min after administration.Then,intensity of fluorescence signals increased progressively over the time and achieved maximum accumulation at 2 h post-injection.The pathologic results showed great biocompatibility.Conclusion TfAu NCs exhibit excellent tumour-targeting ability,which were realized by maintaining the bio-function of Tf,intense NIR fluorescence,and great biocompatibility,which are

关 键 词：金纳米簇 转铁蛋白 体内 靶向成像 前列腺癌 

分 类 号：R737.25[医药卫生—肿瘤] R730.44[医药卫生—临床医学]