Duke University, Department of Chemistry, Durham, North Carolina, United States.
Duke University, Department of Radiology, Durham, North Carolina, United States.
J Biomed Opt. 2019 Apr;24(5):1-13. doi: 10.1117/1.JBO.24.5.051414.
More people die from melanoma after a stage I diagnosis than after a stage IV diagnosis, because the tools available to clinicians do not readily identify which early-stage cancers will be aggressive. Near-infrared pump-probe microscopy detects fundamental differences in melanin structure between benign human moles and melanoma and also correlates with metastatic potential. However, the biological mechanisms of these changes have been difficult to quantify, as many different mechanisms can contribute to the pump-probe signal. We use model systems (sepia, squid, and synthetic eumelanin), cellular uptake studies, and a range of pump and probe wavelengths to demonstrate that the clinically observed effects come from alterations of the aggregated mode from "thick oligomer stacks" to "thin oligomer stacks" (due to changes in monomer composition) and (predominantly) deaggregation of the assembled melanin structure. This provides the opportunity to use pump-probe microscopy for the detection and study of melanin-associated diseases.
更多人死于 I 期诊断后的黑色素瘤，而不是死于 IV 期诊断后的黑色素瘤，因为临床医生可用的工具并不能轻易识别哪些早期癌症具有侵袭性。近红外泵浦探针显微镜可以检测出良性人类痣和黑色素瘤之间黑色素结构的基本差异，并且还与转移潜能相关。然而，这些变化的生物学机制很难被量化，因为许多不同的机制都可能对泵浦探针信号产生贡献。我们使用模型系统（乌贼墨、鱿鱼墨和合成真黑色素）、细胞摄取研究以及一系列泵浦和探针波长来证明，临床上观察到的效果来自于聚集态的改变，从“厚寡聚物堆叠”到“薄寡聚物堆叠”（由于单体组成的变化），以及（主要）组装的黑色素结构的解聚。这为使用泵浦探针显微镜来检测和研究与黑色素相关的疾病提供了机会。
