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.

项目概要 尤其是乳腺癌，具有很强的异质性，具有许多形态和分子特征 不同患者的情况不同。未能充分了解跨肿瘤的分子表达和肿瘤异质性 患者的肿瘤可能导致无效的治疗，从而增加患者的发病率和医疗保健 成本。组学时代使得鉴定几种与乳腺癌有关的新分子标记物成为可能 发育、生存、侵袭，甚至预测治疗反应。我们目前缺乏一种简单的方法来获取 高内容分子信息，同时提供患者肿瘤的高分辨率空间分析。这 该提案旨在为医生提供一种全新的多重分子成像策略，该策略具有潜力 在单个组织学图像中提供高内容分子表达和空间分析。拉曼 光谱学与表面增强拉曼散射 (SERS) 纳米颗粒相结合是一种光学成像 该技术可以为以下领域提供无与伦比的灵敏度（fM 数量级）和复用能力 组织学成像有可能在微观水平上提供丰富的分子细节。临床医生将 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 病理工作流程可以使医生更好地了解患者的肿瘤类型并对患者进行分层 接受尽可能最有效的治疗方案。这种独特的组织学成像策略还具有 有潜力识别患者组织样本中的新分子趋势，可用于预测攻击性 他们的肿瘤状况或患者对特定疗法的反应可能如何。这种创新的离体诊断 策略具有很高的临床转化可能性；为多个组织提供快速全组织切片成像 同时进行生物标志物。我们的方法首先是开发一套新的敏感 SERS 纳米颗粒 (NP) 批次，每个批次都设计有独特的光谱条形码，以便能够同时对整个批次进行分子询问 单个图像内的组织样本。在我们新开发的多重 SERS 的制造和表征之后 纳米颗粒，我们将测试它们在各种乳腺癌中的多重成像能力和肿瘤靶向效率 模型包括细胞培养和未识别的组织切片。我们的纳米颗粒将主动瞄准多个乳房 通过化学缀合靶向配体的癌症受体。我们将评估肿瘤靶向效率 我们新开发的纳米粒子与显微拉曼成像工具并与金标准进行比较 免疫组织化学 (IHC) 染色。这些结果将是这一新药临床转化的重要一步 多重拉曼成像方法；提供给定肿瘤的快速空间分子分析，同时使 为患者提供更有效的个性化治疗。

项目成果

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

NIR 共振和非共振拉曼报告基因在生物成像应用中的多重潜力。

• DOI: 10.1039/d3an01298k
• 发表时间: 2023-10-18
• 期刊: The Analyst
• 作者: O. Eremina;Sarah Schaefer;Ale;er T Czaja;er;Samer Awad;Matthew A Lim;Cristina Zavaleta
• 通讯作者: Cristina Zavaleta