Targeting Metastatic Oral Cancer with Dual-Modal Metallic Nanoparticles

用双模态金属纳米颗粒靶向转移性口腔癌

• 批准号: 7677703
• 负责人: Kvar C Black
• 金额: $ 3.73万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677703
• 关键词: Ablation; Acidity; Adhesives; Alloys; Antibodies; Basement membrane; Binding; Biological Markers; Biomimetics; Biotin; CXCR4 gene; Cell Line; Cell physiology; Cell surface; Cells; Cellular Structures; Cessation of life; Chronic; Clinical; Clinical Treatment; Contrast Media; Detection; Diagnosis; Diagnostic; Diagnostic Imaging; Environment; Epidermal Growth Factor Receptor; Fiber Optics; Glucose Transporter; Glycolysis; Goals; Gold; Head and neck structure; Hypoxia; Image; In Vitro; Incubated; Individual; Induced Hyperthermia; Intervention; Invaded; Ions; Lasers; Lead; Link; Malignant Neoplasms; Marines; Mediating; Metals; Microscope; Modality; Molecular Target; Morbidity - disease rate; Mussels; Neoplasm Metastasis; Operative Surgical Procedures; Optics; Oral; Peptides; Phenotype; Physiological; Play; Polyethylene Glycols; Polymers; Population; Primary Neoplasm; Process; Proliferating; Proton Pump; Research; Resistance; Resolution; Role; Scheme; Secondary to; Shapes; Signal Transduction; Silver; Site; Specificity; Squamous cell carcinoma; Staging; Streptavidin; Structure; Surface; Surface Plasmon Resonance; Surgeon; Survivors; System; Technology; Therapeutic; Therapeutic Agents; Thoracica; Tissues; adhesive protein (mussel); cancer cell; chemokine receptor; extracellular; high risk; luminescence; malignant mouth neoplasm; meetings; mortality; mouth squamous cell carcinoma; nanocrystal; nanoparticle; novel; oncology; research study; tumor; tumorigenesis; two-photon

DESCRIPTION (provided by applicant): Squamous cell carcinomas (SCC) encompass 90% of oral malignancies, which are the eighth most common cancer worldwide. Even with recent advances in oncology and surgery, mortality rates remain high. Often, end stage fatality is associated with the process of metastasis, where malignant cells invade the local basement membrane and move to secondary sites. Therefore, specific detection and destruction of metastatic cells and processes are important goals in undermining the morbidity caused by oral SCC. This research seeks to provide diagnosis and treatment of metastatic oral SCC with metallic nanoparticles functionalized with synthetic polymers containing metal-binding and cancer-targeting motifs. Metal-binding peptides inspired by macromolecular adhesives used by the mussel and barnacle will be employed for immobilizing a polymer linked to cancer-targeting structures to facilitate binding to gold and silver nanocrystals. Antibodies for the epidermal growth factor receptor (EGFR), a current clinical biomarker and over expressed in as many as 80% of oral, head, and neck SCCs, will be used as the targeting structure. Potentially, other cancer biomarkers such as cell surface peptides specific to oral SCC, the CXCR4 chemokine receptor, and glucose transporters could be targeted with the same adhesive scheme to increase specificity of metastatic phenotype targeting schemes. Anti-EGFR antibodies and metal-binding peptides will be linked to polyethylene glycol (PEG) polymers and used to form EGFR-targeting metallic nanoparticles. Their surface plasmon resonance will be tuned into the near-infrared (NIR), a region well suited to oral SCC because of accessibility to conventional and fiber optic technology in clinical use, through control over the shape, size, and composition of the metallic crystals. In vitro targeting experiments will be performed with these dual-modal (diagnostic and therapeutic) plasmonic agents on SCC4, SSC15, and SSC25 cell lines, where the metallic nanoparticles will act as optical contrast and photothermal therapeutic agents in a confocal microscope imaging system. More specifically, this proposal will seek to achieve imaging and photothermal ablation of individual, metastatic cells, a goal that if met could lead to clinical treatment modalities, where surgeons could identify and ablate high-risk cells with a single vehicle.

描述（由申请人提供）：鳞状细胞癌（SCC）涵盖90%的口腔恶性肿瘤，是全球第八大常见癌症。即使肿瘤学和外科手术取得了最新进展，死亡率仍然很高。通常，终末期死亡与转移过程相关，其中恶性细胞侵入局部基底膜并移动到继发部位。因此，特异性检测和破坏转移性细胞和过程是降低口腔鳞状细胞癌发病率的重要目标。本研究旨在提供诊断和治疗转移性口腔SCC与金属纳米粒子功能化的合成聚合物含有金属结合和癌症靶向基序。受贻贝和藤壶使用的大分子粘合剂的启发，金属结合肽将用于固定与癌症靶向结构连接的聚合物，以促进与金和银纳米晶体的结合。表皮生长因子受体（EGFR）是目前的临床生物标志物，在多达80%的口腔、头部和颈部SCC中过度表达，其抗体将用作靶向结构。潜在地，其他癌症生物标志物如对口腔SCC特异性的细胞表面肽、CXCR4趋化因子受体和葡萄糖转运蛋白可以用相同的粘附方案靶向，以增加转移表型靶向方案的特异性。抗EGFR抗体和金属结合肽将与聚乙二醇（PEG）聚合物连接并用于形成EGFR靶向金属纳米颗粒。它们的表面等离子体共振将被调谐到近红外（NIR），这是一个非常适合口腔SCC的区域，因为通过控制金属晶体的形状、大小和组成，可以在临床上使用传统和光纤技术。体外靶向实验将用这些双模式（诊断和治疗）等离子体试剂在SCC 4、SSC 15和SSC 25细胞系上进行，其中金属纳米颗粒将在共聚焦显微镜成像系统中充当光学对比剂和光热治疗剂。更具体地说，该提案将寻求实现单个转移细胞的成像和光热消融，如果实现这一目标，可能会导致临床治疗模式，其中外科医生可以用单一载体识别和消融高风险细胞。