Targeting Metastatic Oral Cancer with Dual-Modal Metallic Nanoparticles

描述（由申请人提供）：鳞状细胞癌（SCC）占口腔恶性肿瘤的90%，是全球第八大常见癌症。即使肿瘤学和外科最近取得了进展，死亡率仍然很高。通常，终末期死亡与转移过程有关，恶性细胞侵入局部基底膜并转移到继发部位。因此，特异性检测和破坏转移细胞和过程是降低口服SCC引起的发病率的重要目标。本研究旨在利用含有金属结合和癌症靶向基元的合成聚合物功能化的金属纳米颗粒来诊断和治疗转移性口服鳞状细胞癌。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相连的聚合物，以促进与金和银纳米晶体的结合。表皮生长因子受体（EGFR）抗体将被用作靶向结构，EGFR是一种目前的临床生物标志物，在多达80%的口腔、头部和颈部SCCs中过表达。潜在地，其他癌症生物标志物，如口服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，并用于形成靶向egfr的金属纳米颗粒。通过控制金属晶体的形状、大小和组成，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，因为在临床使用中可以使用传统和光纤技术。体外靶向实验将在SCC4、SSC15和SSC25细胞系上使用这些双模态（诊断和治疗）等离子体制剂进行，其中金属纳米颗粒将在共聚焦显微镜成像系统中作为光学造影剂和光热治疗剂。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，外科医生可以用单一载体识别和消融高风险细胞。

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.