Dissecting the Molecular Mechanism of Apoptosis during Photothermal Therapy Using Gold Nanoprisms
Dissecting the Molecular Mechanism of Apoptosis during Photothermal Therapy Using Gold Nanoprisms
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DOI：
10.1021/nn505468v
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发表时间：
2015-01-01
期刊：
影响因子：
17.1
通讯作者：
de la Fuente, Jesus M.
中科院分区：
文献类型：
--
作者：
Perez-Hernandez, Marta;del Pino, Pablo;de la Fuente, Jesus M.
等离子体纳米材料的光热响应可以用于诊断（生物传感和光声成像）和治疗（药物递送和光热治疗）中的许多生物医学应用。对使用等离子体纳米材料的光热癌症治疗（实体瘤消融）的最常见的细胞反应是坏死，这是一种将细胞内成分释放到细胞外环境中的过程，产生有害的炎症反应。在这里，我们报告了使用激光诱导光热疗法，采用金纳米棱镜（NPRs），以特异性地诱导细胞凋亡的小鼠胚胎成纤维细胞与SV 40病毒转化。激光照射的热NPR激活细胞凋亡的内在/线粒体途径（程序性细胞死亡），这是由核编码的蛋白质巴克和Bax通过激活仅BH 3蛋白Bid介导的。我们证实，细胞凋亡机制是负责显示如何NPR介导的细胞死亡是依赖于caspase-9和caspase-3蛋白的存在。选择性诱导凋亡细胞死亡和理解后续机制的能力为预测和优化基于NP的光热疗法以治疗患有化疗和放射抗性的癌症患者提供了基础。
The photothermal response of plasmonic nanomaterials can be exploited for a number of biomedical applications in diagnostics (biosensing and optoacoustic imaging) and therapy (drug delivery and photothermal therapy). The most common cellular response to photothermal cancer treatment (ablation of solid tumors) using plasmonic nanomaterials is necrosis, a process that releases intracellular constituents into the extracellular milieu producing detrimental inflammatory responses. Here we report the use of laser-induced photothermal therapy employing gold nanoprisms (NPRs) to specifically induce apoptosis in mouse embryonic fibroblast cells transformed with the SV40 virus. Laser-irradiated hot NPRs activate the intrinsic/mitochondrial pathway of apoptosis (programmed cell death), which is mediated by the nuclear-encoded proteins Bak and Bax through the activation of the BH3-only protein Bid. We confirm that an apoptosis mechanism is responsible by showing how the NPR-mediated cell death is dependent on the presence of caspase-9 and caspase-3 proteins. The ability to selectively induce apoptotic cell death and to understand the subsequent mechanisms provides the foundations to predict and optimize NP-based photothermal therapy to treat cancer patients suffering from chemo- and radioresistance.