A pH Responsive Transistor-like Nanoprobe for Sensitive Detection of Unknown Primary Cancers of the Head and Neck

pH 响应型晶体管纳米探针，用于灵敏检测头颈部未知原发性癌症

• 批准号: 10631041
• 负责人: Baran D Sumer
• 金额: $ 56.05万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631041
• 关键词: Acidosis; Address; Adjuvant Therapy; Aerodigestive Tract; Avidity; Basement membrane; Biopsy; Blood Vessels; Cancer Detection; Cancer Patient; Caring; Cells; Chemotherapy and/or radiation; Clinical; Darkness; Data; Detection; Endoscopes; Epithelium; Excision; FDA approved; Fluorescence; Freezing; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Histologic; Histology; Histopathology; Human Papillomavirus; Image; Impairment; Indocyanine Green; Inflammatory; Intravenous; Libraries; Light; Lymphatic; Lymphoid Tissue; Malignant Neoplasms; Malignant neoplasm of pharynx; Mediating; Micelles; Modality; Mucous Membrane; Nature; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Pathology; Patient-Focused Outcomes; Patients; Pharyngeal structure; Phase; Phase II Clinical Trials; Phase Transition; Physical Examination; Polymers; Positron-Emission Tomography; Primary Neoplasm; Prognosis; Quality-Adjusted Life Years; Sensitivity and Specificity; Serious Adverse Event; Staging; Stains; Surface; Tail; Testing; Time; Tissues; Tonsil; Tonsillar Tissue; Tonsillectomy; Transistors; Validation; Veins; X-Ray Computed Tomography; amphiphilicity; aqueous; cancer diagnosis; detection sensitivity; fluorodeoxyglucose; functional improvement; head and neck cancer patient; human tissue; improved; in vivo fluorescence; intravenous administration; intravenous injection; invention; lymph nodes; lymphocyte proliferation; meter; millimeter; nanoprobe; optimal treatments; overtreatment; standard of care; targeted treatment; tumor; tumor microenvironment; viral detection

A pH Responsive Transistor-like Nanoprobe for Sensitive Detection of Unknown Primary Cancers of the Head and Neck Project Summary/Abstract Approximately 65,000 cases of Head and Neck Squamous Cell Cancer (HNSCC) are diagnosed each year in the US and arise in the mucosal lining of the upper aerodigestive tract and spread to local lymph nodes. In some cases, the primary tumor is too small to be detected, with enlarged nodes being the only manifestation of HNSCC. These unknown primary cancers (UPCs), often induced by human papilloma virus (HPV), usually arise in the mucosa of Waldeyer's ring, the lymphatic tonsillar tissues of the pharynx. Finding UPC is significant and impactful addressing an unmet need with long term oncologic and functional outcomes improved by locating and removing UPC. However, their detection is impaired by the corrugated, cryptic surface, and nodularity of lymphatic tissue which decreases the sensitivity of physical examination while the vascularity and fluorodeoxyglucose (FDG) avidity of the lymphoid tissue obscure small tumors by computerized tomography (CT) and positron emission tomography (PET). We have invented a library of ultra pH sensitive (UPS) nanoprobes, covalently conjugated to indocyanine green (ICG) that respond to acidic tumor microenvironment, with a concomitant sharp change in their fluorescence state from OFF to ON. One such nanoprobe, ONM-100, has been developed and studied in a Phase 1 and ongoing FDA approved Phase 2 clinical trial. it has been shown to be well tolerated with no serious adverse events, compatible with surgical endoscopes, and able to detect a variety of cancers including HNSCC in real time. Based on these data we hypothesize that ONM-100 used as an adjunct to SOC panendoscopy can improve detection of UPC. To test our hypothesis, we will (1) Compare the sensitivity and specificity of activatable probe ONM-100 for cancer detection to always ON probes for tumors in Waldeyer's ring; (2) Detect HPV-mediated HNSCC in patients after systemic administration of ONM-100 comparing fluorescence to true-positive cancers; (3) Detect UPC in patients after systemic administration of ONM-100. Successful execution of this project will provide precise excision of UPC and avoidance of intense adjuvant therapy for UPC patients significantly improving care and outcomes for these patients who suffer greatly from less oncologically effective imprecise overtreatment.

pH响应式晶体管样纳米探针，用于敏感的未知主要检测 头部和颈部的癌 项目摘要/摘要 大约65,000例头颈部鳞状细胞癌（HNSCC）为 每年在美国被诊断出来，并在上层机场消化道的粘膜衬里出现 并扩散到局部淋巴结。在某些情况下，原发性肿瘤太小而无法检测到 扩大节点是HNSCC的唯一表现。这些未知的主要癌症 （UPC）通常是由人乳头瘤病毒（HPV）诱导的，通常在Waldeyer的粘膜中出现 环，咽的淋巴扁桃体组织。寻找UPC是重要而有影响力的 通过定位，以长期的肿瘤学和功能结果来满足未满足的需求 并删除UPC。但是，它们的检测受到瓦楞，隐秘的表面和 淋巴组织的结节性降低了体格检查的敏感性 淋巴组织的血管性和荧光脱氧葡萄糖（FDG）造成的小肿瘤掩盖了小肿瘤 计算机断层扫描（CT）和正电子发射断层扫描（PET）。 我们发明了一个超pH敏感（UPS）纳米探针的库，共价连接到 对酸性肿瘤微环境的反应的吲哚烷绿色（ICG），并具有锋利的尖锐 从OFF到ON改变其荧光状态。这样的纳米探针是ONM-100 在第1阶段和正在进行的FDA批准的2阶段临床试验中开发和研究。它一直 证明没有严重的不良事件，与手术内窥镜兼容，可容忍良好 并能够实时检测包括HNSCC在内的各种癌症。根据这些数据，我们 假设将ONM-100用作SOC Panendodoscopicy的辅助检查可以改善对的检测 UPC。为了检验我们的假设，我们将（1）比较可激活的灵敏度和特异性 探针ONM-100癌症检测始终是Waldeyer环中肿瘤的探针； （2） 在全身给药ONM-100进行比较后，检测患者的HPV介导的HNSCC 荧光到真正的阳性癌症； （3）检测全身给药后患者的UPC ONM-100。该项目的成功执行将提供UPC和避免的精确切除 UPC患者的强烈辅助治疗可显着改善这些治疗 肿瘤有效不精确过度治疗的患者遭受了极大的痛苦。