Kim Dong-Hyun, Larson Andrew C
Department of Radiology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA.
Department of Radiology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA; Department of Electrical Engineering and Computer Science, Evanston, IL, USA; Department of Biomedical Engineering, Northwestern University, Chicago, IL, USA; International Institute of Nanotechnology (IIN), Northwestern University, Evanston, IL, USA.
Biomaterials. 2015 Jul;56:154-64. doi: 10.1016/j.biomaterials.2015.03.048. Epub 2015 Apr 17.
We report an approach for simple, reproducible and high-yield synthesis of branched GNPs directed by deoxycholate bile acid supramolecular aggregates in Au solution. A growth process involving stepwise trapping of the GNP seeds and Au ions in the deoxycholate bile acid solution yields multiple-branched GNPs. Upon NIR laser irradiation strong NIR absorption for branched GNPs induced photothermal-heating to destroy tumor cells. Subsequently, these branched GNPs were biofunctionalized with cRGD cell penetrating-targeting peptides for photothermal cancer treatment applications. Branched GNPs conjugated with cRGD peptides enhanced internalization of the branched GNPs in BxPC3 human pancreatic adenocarcinoma cells and effectively ablated BxPC3 cells when irradiated with a NIR laser (808 nm). Their potential use as photothermal transducing agents was demonstrated in in vivo settings using a pancreatic cancer xenograft model. The tumors were effectively ablated with cRGD-branched GNPs injection and laser exposure without any observation of tumor recurrence. This firstly reported method for deoxycholate bile acid directed synthesis of branched GNPs opens new possibilities for the production of strong NIR absorbing nanostructures for selective nano-photothermolysis of cancer cells and the further design of novel materials with customized spectral and structural properties for broader applications.
我们报道了一种在金溶液中由脱氧胆酸超分子聚集体指导的简单、可重复且高产率合成分支状金纳米颗粒(GNPs)的方法。在脱氧胆酸溶液中逐步捕获GNP种子和金离子的生长过程产生了多分支的GNPs。在近红外激光照射下,分支状GNPs强烈的近红外吸收诱导光热加热以破坏肿瘤细胞。随后,这些分支状GNPs用cRGD细胞穿透靶向肽进行生物功能化,用于光热癌症治疗应用。与cRGD肽缀合的分支状GNPs增强了分支状GNPs在BxPC3人胰腺腺癌细胞中的内化,并在近红外激光(808nm)照射时有效地消融了BxPC3细胞。在使用胰腺癌异种移植模型的体内实验中证明了它们作为光热转导剂的潜在用途。通过注射cRGD分支状GNPs并进行激光照射,肿瘤被有效地消融,未观察到任何肿瘤复发。这种首次报道的由脱氧胆酸指导合成分支状GNPs的方法为生产用于癌细胞选择性纳米光热解的强近红外吸收纳米结构以及进一步设计具有定制光谱和结构特性以用于更广泛应用的新型材料开辟了新的可能性。