Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular Media

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Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular Media

机译：肿瘤细胞外介质代谢变化的多重SERS检测

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The composition and intercellular interactions of tumor cells in the tissues dictate the biochemical and metabolic properties of the tumor microenvironment. The metabolic rewiring has a profound impact on the properties of the microenvironment, to an extent that monitoring such perturbations could harbor diagnostic and therapeutic relevance. A growing interest in these phenomena has inspired the development of novel technologies with sufficient sensitivity and resolution to monitor metabolic alterations in the tumor microenvironment. In this context, surface-enhanced Raman scattering (SERS) can be used for the label-free detection and imaging of diverse molecules of interest among extracellular components. Herein, the application of nanostructured plasmonic substrates comprising Au nanoparticles, self-assembled as ordered superlattices, to the precise SERS detection of selected tumor metabolites, is presented. The potential of this technology is first demonstrated through the analysis of kynurenine, a secreted immunomodulatory derivative of the tumor metabolism and the related molecules tryptophan and purine derivatives. SERS facilitates the unambiguous identification of trace metabolites and allows the multiplex detection of their characteristic fingerprints under different conditions. Finally, the effective plasmonic SERS substrate is combined with a hydrogel-based three-dimensional cancer model, which recreates the tumor microenvironment, for the real-time imaging of metabolite alterations and cytotoxic effects on tumor cells.

机译：组织中肿瘤细胞的组成和细胞间相互作用决定了肿瘤微环境的生化和代谢特性。代谢重新布线对微环境的性质产生了深远的影响，在某种程度上，监测此类扰动可能具有诊断和治疗意义。对这些现象的日益浓厚的兴趣激发了具有足够灵敏度和分辨率以监测肿瘤微环境中代谢变化的新技术的发展。在这种情况下，表面增强拉曼散射（SERS）可用于无标记的细胞外组分间感兴趣的各种分子的检测和成像。在本文中，提出了包含自组装成有序超晶格的Au纳米粒子的纳米结构等离激元底物在所选肿瘤代谢物的精确SERS检测中的应用。该技术的潜力首先通过对犬尿氨酸的分析来证明，犬尿氨酸是一种肿瘤代谢的分泌型免疫调节衍生物，并且与相关分子色氨酸和嘌呤衍生物有关。 SERS有助于痕量代谢产物的明确鉴定，并允许在不同条件下对其特征指纹进行多重检测。最后，将有效的等离子SERS底物与基于水凝胶的三维癌症模型相结合，从而重建肿瘤的微环境，以实时成像代谢物变化和对肿瘤细胞的细胞毒性作用。

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《Advanced Functional Materials》 |2020年第17期|1910335.1-1910335.10|共10页
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CIC biomaGUNE BRTA Paseo Miramon 182 Donostia San Sebastian 20014 Spain|CIBER BBN Biomed Res Networking Ctr Bioengn Biomat Donostia San Sebastian 20014 Spain|CIC bioGUNE BRTA Derio 48160 Spain;

CIC biomaGUNE BRTA Paseo Miramon 182 Donostia San Sebastian 20014 Spain|CIBER BBN Biomed Res Networking Ctr Bioengn Biomat Donostia San Sebastian 20014 Spain;

CIC biomaGUNE BRTA Paseo Miramon 182 Donostia San Sebastian 20014 Spain|CIC nanoGUNE Consolider BRTA Donostia San Sebastian 20018 Spain;

CIC bioGUNE BRTA Derio 48160 Spain|CIBERONC Biomed Res Networking Ctr Oncol Derio 48160 Spain;

CIC biomaGUNE BRTA Paseo Miramon 182 Donostia San Sebastian 20014 Spain;

CSIC ICMAB Inst Ciencia Mat Barcelona Bellaterra 08193 Spain;

CIC bioGUNE BRTA Derio 48160 Spain|CIBERONC Biomed Res Networking Ctr Oncol Derio 48160 Spain|Univ Basque Country UPV EHU Biochem & Mol Biol Dept Bilbao 48940 Spain|Ikerbasque Basque Fdn Sci Bilbao 48013 Spain;

CIC biomaGUNE BRTA Paseo Miramon 182 Donostia San Sebastian 20014 Spain|CIBER BBN Biomed Res Networking Ctr Bioengn Biomat Donostia San Sebastian 20014 Spain|Ikerbasque Basque Fdn Sci Bilbao 48013 Spain;

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3D hydrogels cancer cell models; plasmonic substrates; surface-enhanced Raman scattering; tumor environment; tumor metabolism sensing;

机译：3D水凝胶癌细胞模型;等离子体底物;表面增强拉曼散射;肿瘤环境;肿瘤代谢感应;

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专利

1. Facilely synthesized polydopamine encapsulated surface-enhanced Raman scattering (SERS) probes for multiplex tumor associated cell surface antigen detection using SERS imaging [J] . Sun Changlong, Zhang Ling, Zhang Ren, RSC Advances . 2015,第88期

机译：简便合成的聚多巴胺封装的表面增强拉曼散射（SERS）探针，用于使用SERS成像进行多重肿瘤相关细胞表面抗原检测
2. Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles [J] . Vanessa Lopes-Rodrigues, Alessio Di Luca, Justyna Mleczko, Scientific reports. . 2017,第1期

机译：鉴定与细胞外囊泡介导的癌症中多药抗性表型相关的代谢改变
3. Bio-Inspired NanoVilli Chips for Enhanced Capture of Tumor-Derived Extracellular Vesicles: Toward Non-Invasive Detection of Gene Alterations in Non-Small Cell Lung Cancer [J] . Dong Jiantong, Zhang Ryan Y., Sun Na, ACS applied materials & interfaces . 2019,第15期

机译：生物启发的纳米米芯片，用于增强肿瘤衍生的细胞外囊囊泡的捕获：朝向非小细胞肺癌基因变化的非侵入性检测
4. Glucose-Functionalized Gold Nanoparticles as a Metabolically Targeted CT Contrast Agent for Distinguishing Tumors from Non-Malignant Metabolically Active Processes [C] . Tamar Dreifuss, Menachem Motiei, Oshra Betzer, Nanoscale imaging, sensing, and actuation for biomedical applications XIV . 2017

机译：葡萄糖功能化金纳米粒子作为代谢靶向CT造影剂，用于区分非恶性代谢活跃过程中的肿瘤
5. Development of SERS based biosensing techniques for multiplexed oligonucleotides and pathogenic bacteria detection. [D] . Sun, Jian. 2010

机译：基于SERS的生物传感技术的发展，用于多重寡核苷酸和病原菌检测。
6. Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles [O] . Vanessa Lopes-Rodrigues, Alessio Di Luca, Justyna Mleczko, -1

机译：鉴定与癌症中多药耐药表型有关的代谢改变及其由细胞外囊泡介导的细胞间转移
7. Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular Media [O] . Javier Plou, Isabel García, Mathias Charconnet, 2020

机译：多重SERs检测肿瘤细胞外培养基中的代谢改变
8. Development of Spontaneous Mammary Tumors in BALB/c-p53+/-Mice: Detection of Early Genetic Alterations and the Mapping of BALB/c Susceptibility Genes [R] . Hill, X. , Jerry, J. 2005

机译：BaLB / c-p53 +/-小鼠自发性乳腺肿瘤的发展：早期遗传改变的检测和BaLB / c易感基因的定位

Multiplex SERS Detection of Metabolic Alterations in Tumor Extracellular Media

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