Supplement to Support the Development of a New Multiplexed Imaging Tool using Raman Spectroscopy for Breast Cancer

支持开发使用拉曼光谱治疗乳腺癌的新型多重成像工具的补充材料

• 批准号: 10839117
• 负责人: Cristina L. Zavaleta
• 金额: $ 6.55万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-16 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10839117
• 关键词: Affinity; Antibody Avidity; Bar Codes; Binding; Biological Markers; Breast Cancer Patient; Cellular Assay; Charge; Chemicals; Clinical; Collection; Consumption; Contrast Media; Detection; Development; Diagnosis; Disease; Ensure; Failure; Gold; Health Care Costs; Histology; Image; Imaging Device; Imaging Techniques; Immunotherapy; In Vitro; Individual; Ligands; Maps; Molecular; Molecular Profiling; Monoclonal Antibodies; Morbidity - disease rate; Nanosphere; Oncologist; Pathologist; Pathology; Patient-Focused Outcomes; Patients; Physicians; Prediction of Response to Therapy; Property; Proteins; Public Health; Raman Spectrum Analysis; Regimen; Research; Sampling; Silicon Dioxide; Specimen; Stains; Surface; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Woman; antibody conjugate; cancer cell; career development; chemical property; clinical application; clinical translation; contrast imaging; design; detection sensitivity; effective therapy; imaging approach; improved; individual patient; ineffective therapies; malignant breast neoplasm; molecular imaging; multiplexed imaging; nanoparticle; neoplastic cell; novel; optical imaging; overexpression; pathology imaging; patient stratification; predicting response; programmed cell death ligand 1; programmed cell death protein 1; receptor expression; side effect; single cell analysis; spectrograph; targeted biomarker; targeted treatment; therapeutically effective; tool; treatment optimization; treatment response; tumor; tumor heterogeneity

Project Summary Breast cancer, in particular, is very heterogeneous with many morphological and molecular features that present differently across patients. Failure to fully understand the molecular expression and tumor heterogeneity across a patient's tumor can lead to administration of ineffective therapies that increase patient morbidity and healthcare costs. The -omics era has made it possible to identify several new molecular markers involved in breast cancer development, survival, invasion and even predicting treatment response. We currently lack an easy way to obtain high content molecular information while providing high resolution spatial profiling across a patient's tumor. This proposal aims to provide physicians with an entirely new multiplexed molecular imaging strategy that has the potential to offer both high content molecular expression and spatial profiling in a single histology image. Raman spectroscopy in conjunction with surface enhanced Raman scattering (SERS) nanoparticles is an optical imaging technique that can offer unsurpassed sensitivity (on the order of fM) and multiplexing capabilities to the field of histology imaging with the potential to provide rich molecular details on the microscopic level. Clinicians will be able to utilize the imaging strategy on the same tissue sections prepared for histology. Incorporating it into the pathology workfiow could enable physicians to better understand the patient's tumor type and stratify patients to receive the most effective therapeutic regimen possible. This unique histology imaging strategy also has the potential to identify new molecular trends in patient's tissue samples that could be used to predict how aggressive their tumor is or how well the patient is likely to respond to given therapies. This innovative ex-vivo diagnostic strategy has a high likelihood for clinical translation; offering rapid whole tissue section imaging for multiple biomarkers simultaneously. Our approach begins by developing a new set of sensitive SERS nanoparticle (NP) batches, each designed with a unique spectral barcode to enable simultaneous molecular interrogation of an entire tissue sample within a single image. After fabrication and characterization of our newly developed multiplexed SERS nano particles, we will test their multiplexed imaging capabilities and tumor targeting efficiency in various breast cancer models including cell culture and on de-identified tissue sections. Our nanoparticles will actively target multiple breast cancer receptors through chemically conjugated targeting ligands. We will assess the tumor targeting efficiency of our newly developed nanoparticles with microscopic Raman imaging tools and compare with gold standard immunohistochemistry {IHC) staining. These results will be an important step in the clinical translation of this new multiplexed Raman imaging approach; to provide rapid spatial molecular profiling of a given tumor while enabling a more effective personalized therapy to the patient.

项目摘要 尤其是乳腺癌，非常异质，具有许多形态和分子特征 各种患者的态度不同。未能完全理解跨A的分子表达和肿瘤异质性 患者的肿瘤会导致无效疗法的给药，从而增加患者的发病率和医疗保健 费用。 -omics时代使鉴定乳腺癌涉及的几个新分子标记成为可能 发育，生存，入侵，甚至预测治疗反应。我们目前缺乏一种简单的方法 高含量的分子信息，同时在患者的肿瘤上提供高分辨率的空间分析。这 提案旨在为医生提供具有潜力的全新多重分子成像策略 在单个组织学图像中提供高含量的分子表达和空间分析。拉曼 光谱与表面增强的拉曼散射（SERS）纳米粒子结合使用是光学成像 可以提供无与伦比的灵敏度的技术（按FM的顺序）以及对领域的多重功能 组织学成像，具有在微观水平上提供丰富分子细节的潜力。临床医生会 能够在为组织学准备的相同组织切片上利用成像策略。将其纳入 病理学工作表可以使医生能够更好地了解患者的肿瘤类型并将患者分层 接受最有效的治疗方案。这种独特的组织学成像策略也有 潜力可以鉴定患者组织样品中可用于预测如何侵略性的新分子趋势 它们的肿瘤是或患者对给定疗法有反应的程度。这种创新的前体内诊断 策略对于临床翻译具有很高的可能性；提供多个的快速整体组织成像成像 同时生物标志物。我们的方法首先开发一组新的敏感SERS纳米颗粒（NP） 批处理，每个设计都使用独特的光谱条形码设计，以同时进行整个分子询问 单个图像中的组织样品。在制造和表征我们新开发的多路复用 纳米颗粒，我们将测试各种乳腺癌的多路复用成像能力和肿瘤靶向效率 包括细胞培养和取消识别组织切片的模型。我们的纳米颗粒将积极瞄准多个乳房 通过化学共轭靶向配体的癌症受体。我们将评估肿瘤的靶向效率 我们新开发的纳米颗粒具有微观拉曼成像工具，并与黄金标准进行比较 免疫组织化学{IHC）染色。这些结果将是该新的临床翻译中的重要一步 多路复用拉曼成像方法；在启用时提供给定肿瘤的快速空间分子分析 对患者的更有效的个性化疗法。

项目成果

Multiplexing potential of NIR resonant and non-resonant Raman reporters for bio-imaging applications.

• DOI: 10.1039/d3an01298k
• 发表时间: 2023-10
• 期刊: The Analyst
• 作者: O. Eremina;Sarah Schaefer;Alexander T Czaja;Samer Awad;Matthew A Lim;Cristina Zavaleta