Targeting Metastatic Oral Cancer with Dual-Modal Metallic Nanoparticles

描述(申请人提供)：鳞状细胞癌(SCC)包括90%的口腔恶性肿瘤，这是世界第八大最常见的癌症。即使最近肿瘤学和外科手术取得了进展，死亡率仍然很高。通常，终末期的病死率与转移过程有关，在转移过程中，恶性细胞侵入局部基底膜并转移到继发部位。因此，对转移细胞和转移过程的特异性检测和破坏是降低口腔鳞癌发病率的重要目标。这项研究旨在通过含有金属结合基序和肿瘤靶向基序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腔鳞状细胞癌。受贻贝和藤壶使用的大分子粘合剂启发的金属结合肽将被用于固定连接到癌症靶向结构的聚合物，以促进与金和银纳米晶体的结合。表皮生长因子受体(EGFR)的抗体是目前临床上的一种生物标志物，在多达80%的口腔、头部和颈部SCC中过度表达，将被用作靶向结构。潜在地，其他癌症生物标志物，如口腔鳞状细胞癌特异性细胞表面肽、CXCR4趋化因子受体和葡萄糖转运体，可以通过相同的粘合方案进行靶向，以提高转移表型靶向方案的特异性。抗EGFR抗体和金属结合肽将被连接到聚乙二醇(PEG)聚合物上，并用于形成靶向EGFR的金属纳米颗粒。他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鳞状细胞癌的区域，因为通过控制金属晶体的形状、大小和组成，临床上可以使用传统和光纤技术。这些双模式(诊断和治疗)等离子体试剂将在SCC4、SSC15和SSC25细胞系上进行体外靶向实验，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，这项提议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工具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.