Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
Skolkovo Institute of Science and Technology, Moscow, Russia.
Sci Rep. 2019 Aug 27;9(1):12439. doi: 10.1038/s41598-019-48335-6.
Photoswitchable fluorescent proteins (PFPs) that can change fluorescence color upon excitation have revolutionized many applications of light such as tracking protein movement, super-resolution imaging, identification of circulating cells, and optical data storage. Nevertheless, the relatively weak fluorescence of PFPs limits their applications in biomedical imaging due to strong tissue autofluorecence background. Conversely, plasmonic nanolasers, also called spasers, have demonstrated potential to generate super-bright stimulated emissions even inside single cells. Nevertheless, the development of photoswitchable spasers that can shift their stimulated emission color in response to light is challenging. Here, we introduce the novel concept of spasers using a PFP layer as the active medium surrounding a plasmonic core. The proof of principle was demonstrated by synthesizing a multilayer nanostructure on the surface of a spherical gold core, with a non-absorbing thin polymer shell and the PFP Dendra2 dispersed in the matrix of a biodegradable polymer. We have demonstrated photoswitching of spontaneous and stimulated emission in these spasers below and above the spasing threshold, respectively, at different spectral ranges. The plasmonic core of the spasers serves also as a photothermal (and potentially photoacoustic) contrast agent, allowing for photothermal imaging of the spasers. These results suggest that multimodal photoswitchable spasers could extend the traditional applications of spasers and PFPs in laser spectroscopy, multicolor cytometry, and theranostics with the potential to track, identify, and kill abnormal cells in circulation.
光可切换荧光蛋白（PFPs）在受到激发时可以改变荧光颜色，这一特性革新了许多应用光的领域，如追踪蛋白质运动、超分辨率成像、循环细胞的识别以及光数据存储。然而，PFPs 的相对较弱的荧光限制了它们在生物医学成像中的应用，因为组织的自发荧光背景较强。相反，等离子体纳米激光器，也称为“spasers”，已经证明了即使在单个细胞内也能产生超强亮度受激发射的潜力。然而，开发能够响应光而改变受激发射颜色的光可切换 spasers 具有挑战性。在这里，我们提出了一种新的概念，即使用 PFP 层作为等离子体核周围的活性介质来制造 spasers。通过在球形金核的表面上合成多层纳米结构，证明了这一原理，该多层纳米结构具有非吸收性的薄聚合物壳和分散在可生物降解聚合物基质中的 PFP Dendra2。我们已经证明了在不同光谱范围内，spasers 低于和高于受激发射阈值时，自发和受激发射都可以进行光切换。spasers 的等离子体核还可用作光热（和潜在的光声）造影剂，从而可以对 spasers 进行光热成像。这些结果表明，多模态光可切换 spasers 可以扩展 spasers 和 PFPs 在激光光谱学、多色细胞计数学和治疗学中的传统应用，具有在循环中跟踪、识别和杀死异常细胞的潜力。
