Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.
J Am Chem Soc. 2016 Feb 3;138(4):1258-64. doi: 10.1021/jacs.5b10997. Epub 2016 Jan 25.
Plasmonic nanoparticles are increasingly utilized in biomedical applications including imaging, diagnostics, drug delivery, and plasmonic photothermal therapy (PPT). PPT involves the rapid conversion of light into heat by plasmonic nanoparticles targeted to a tumor, causing hyperthermia-induced cell death. These nanoparticles can be passively targeted utilizing the enhanced permeability and retention effect, or actively targeted using proteins, peptides, or other small molecules. Here, we report the use of actively targeted spherical gold nanoparticles (AuNPs), both to induce PPT cell death, and to monitor the associated molecular changes through time-dependent surface enhanced Raman spectroscopy within a single cell. We monitored these changes in real-time and found that heat generated from the aggregated nanoparticles absorbing near-infrared (NIR) laser light of sufficient powers caused modifications in the protein and lipid structures within the cell and ultimately led to cell death. The same molecular changes were observed using different nanoparticle sizes and laser intensities, indicating the consistency of the molecular changes throughout PPT-induced cell death from actively targeted AuNPs. We also confirmed these observations by comparing them to reference spectra obtained by cell death induced by oven heating at 100 °C. The ability to monitor PPT-induced cell death in real-time will help understand the changes on a molecular level and offers us a basis to understand the molecular mechanisms involved in photothermal cancer cell death.
等离子体纳米粒子在生物医学应用中越来越受欢迎，包括成像、诊断、药物输送和等离子体光热治疗 (PPT)。PPT 涉及将光迅速转化为热能，通过针对肿瘤的等离子体纳米粒子实现，导致热诱导细胞死亡。这些纳米粒子可以通过增强的通透性和保留效应被动靶向，也可以使用蛋白质、肽或其他小分子主动靶向。在这里，我们报告了使用主动靶向的球形金纳米粒子 (AuNP)，既可以诱导 PPT 细胞死亡，也可以通过时间相关的表面增强拉曼光谱在单个细胞内监测相关的分子变化。我们实时监测这些变化，发现吸收足够功率近红外 (NIR) 激光光的聚集纳米粒子产生的热量导致细胞内蛋白质和脂质结构发生变化，最终导致细胞死亡。使用不同的纳米粒子尺寸和激光强度观察到相同的分子变化，表明从主动靶向 AuNP 诱导的 PPT 细胞死亡过程中分子变化的一致性。我们还通过将其与通过在 100°C 下烘烤引起的细胞死亡获得的参考光谱进行比较来证实这些观察结果。实时监测 PPT 诱导的细胞死亡的能力将有助于我们在分子水平上理解这些变化，并为我们理解光热癌症细胞死亡涉及的分子机制提供了基础。
