Abstract：
Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανβ3-integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.
摘要：
光学成像和光谱模式目前对于体内癌症检测和图像引导手术具有相当大的兴趣。但是生物医学组织的浑浊或散射性质严重限制了它们检测埋藏或闭塞肿瘤病变的能力。在这里，我们报告了基于胶体金纳米星（AuNSs）的双模态等离子体纳米结构的开发，用于同时表面增强拉曼散射（SERS）和光声（PA）检测体外动物组织中嵌入（隐藏）的肿瘤体模。通过使用红细胞膜作为天然来源的仿生涂层，我们表明，这类双模态造影剂可以提供拉曼光谱和PA信号，用于检测和区分隐藏的实体瘤，并大大改善了组织穿透深度。与以前的聚合物涂层AuNS相比，当暴露于人血浆时,仿生涂层还能够最小化蛋白质吸附和细胞摄取,而不损害其SERS或PA信号。我们进一步显示，肿瘤靶向肽（例如环状RGD）可以非共价插入，用于靶向转移癌细胞上表达的ανβ3整联蛋白受体，并通过SERS和PA成像（PAI）进行跟踪。最后,我们展示了模拟肿瘤的体模的图像引导切除，其中包括埋藏在皮肤和脂肪组织层（厚度为6mm）下的转移性肿瘤细胞。具体来说,PAI用于确定精确的肿瘤位置，而SERS光谱信号用于肿瘤鉴定和分化。这项工作打开了使用这些具有优异信号和生物稳定性的仿生双模态纳米颗粒用于术中癌症检测和切除的可能性。
