Photothermal Method for Diagnostics and Selective Nano-thermolysis of Superficial

用于表面诊断和选择性纳米热解的光热方法

• 批准号: 7660944
• 负责人: Jason Howard Hafner
• 金额: $ 20.13万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7660944
• 关键词: Antibodies; Area; Binding; Cells; Chemicals; Collection; Coupling; Cutaneous; Cytolysis; Detection; Development; Diagnostic; Diagnostic Procedure; Diffuse; EGF gene; Electrons; Endocytosis; Epidermal Growth Factor Receptor; Excision; Fiber; Fluorescence; Generations; Gold; Head and Neck Squamous Cell Carcinoma; Image; In Situ; In Vitro; Individual; Lasers; Lesion; Life; Malignant Epithelial Cell; Malignant Neoplasms; Measures; Mechanics; Methods; Microscope; Microscopy; Molecular Target; Monitor; Monoclonal Antibodies; Monoclonal Antibody C225; Mucous Membrane; Normal Cell; Operative Surgical Procedures; Optics; Outcome; Patients; Physiologic pulse; Probability; Process; Property; Protocols documentation; Pump; Radiation; Research; Safety; Scanning; Signal Transduction; Skin; Specificity; Squamous cell carcinoma; Structure; Surface; Technology; Temperature; Time; Tissues; Topical application; Validation; alternative treatment; cancer cell; cancer therapy; cell injury; cytotoxicity; follow-up; in vivo; monolayer; nano; nanoparticle; neoplastic cell; optical fiber; public health relevance; software development; targeted delivery; treatment strategy; tumor; vector

DESCRIPTION (provided by applicant): The proposed project is aimed at the development of Laser Activated Nano-Thermolysis as Cell Elimination Technology (LANTCET) for chemical-free detection and selective destruction (elimination) of tumor cells in superficial tissue layer and with single-cell selectivity thus excluding the damage to collateral normal cells. LANTCET includes four major steps: (1) topical application of non-toxic conjugates of gold nanoparticles (NP) with follow up selective formation of intracellular NP clusters due to endocytosis; (2) optical detection of tumor cells in tissue with normal cells by registering NP cluster-specific optical scattering signals, (3) selective mechanical destruction (thermolysis) of individual tumor cells by pulsed laser-induced photo-thermal intracellular micro- bubbles (PTB) selectively generated around NP clusters in target cells, and (4) real-time optical guidance of tumor cell damage by detecting (imaging) the PTB-specific scattering optical signals. The detection, destruction and optical guidance processes are completed within microseconds and with one devise. The efficacy, specificity and selectivity of the LANTCET is provided by NP cluster - PT bubble mechanism of cell optical detection and destruction that concentrates all absorbed laser energy within individual tumor cells and thus excludes thermal damage of normal cells and tissues. Optical monitoring of NP clusters and PTBs in a tissue layer will guide the ablative laser pulse to the tumor cell and help to determine optimal laser fluence for the 100% damage of tumor cells and real-time optical validation of tumor destruction. PUBLIC HEALTH RELEVANCE: Superficial cancers such as cutaneous tumors and early lesions of the mucosa of the upper aerodigestive tract are most often treated by surgical excision. However for diffuse areas of the skin or for mucosa in functionally or cosmetically important structures, surgical excision can be extremely morbid. Consequently, the development of alternative treatment strategies that more selectively target neoplastic cells could enhance outcomes for patients with these tumor types. The advent of molecularly targeted cancer therapy has shown significant promise with a recently completed trial showing a survival benefit when a monoclonal antibody that binds to the Epidermal Growth Factor Receptor (EGFR), which is highly expressed by some cancer cells, is used for the treatment of squamous cell carcinoma of the upper aerodigestive tract (SCCHN). The nearly simultaneous development of gold nanoparticles which can be optically activated in situ to generate the intracellular photothermal bubbles (PTB) suggests that coupling molecular targets of tumor cells with nanoparticles for activation of intracellular PTB could serve as an effective strategy for detecting and treating cancer at cell level.

描述(申请人提供)：建议的项目旨在开发激光激活纳米热解作为细胞消除技术(LANTCET)，用于无化学物质检测和选择性破坏(消除)浅组织层的肿瘤细胞，并具有单细胞选择性，从而排除对侧枝正常细胞的损害。LANTCET包括四个主要步骤：(1)局部应用无毒的纳米金颗粒(NP)结合物，后续通过内吞作用选择性形成细胞内NP簇；(2)通过记录NP簇特有的光学散射信号，对正常细胞中的肿瘤细胞进行光学检测；(3)通过脉冲激光诱导的光热细胞内微泡(PTB)选择性地在靶细胞中的NP簇周围产生的光热微泡(PTB)对单个肿瘤细胞进行选择性机械破坏(热分解)；以及(4)通过检测(成像)PTB特有的散射光信号，对肿瘤细胞损伤进行实时光学引导。探测、销毁和光学制导过程在微秒内用一个装置完成。LANTCET的有效性、特异性和选择性是由NP CLUSTER-PT气泡细胞光学检测和破坏机制提供的，该机制将所有吸收的激光能量集中在单个肿瘤细胞内，从而排除正常细胞和组织的热损伤。对组织层中NP簇和PTB的光学监测将引导消融激光脉冲到达肿瘤细胞，并帮助确定100%破坏肿瘤细胞的最佳激光剂量，以及实时光学验证肿瘤破坏。 公共卫生相关性：浅表性癌症，如皮肤肿瘤和上呼吸道粘膜的早期病变，最常通过手术切除来治疗。然而，对于皮肤的弥漫性区域或功能或美容重要结构中的粘膜，手术切除可能是极其病态的。因此，开发更有选择性地针对肿瘤细胞的替代治疗策略可以改善这些肿瘤类型患者的预后。分子靶向癌症治疗的出现显示了巨大的希望，最近完成的一项试验显示，当与某些癌细胞高度表达的表皮生长因子受体(EGFR)结合的单抗用于治疗上呼吸道鳞状细胞癌(SCCHN)时，可以提高生存。金纳米颗粒可以被原位光激活产生细胞内光热气泡(PTB)，几乎同时发展，这表明将肿瘤细胞的分子靶标与激活细胞内PTB的纳米颗粒偶联可以作为一种在细胞水平上检测和治疗癌症的有效策略。