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: 7776896
• 负责人: Jason Howard Hafner
• 金额: $ 16.78万
• 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/7776896
• 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（由申请人提供）：拟议项目旨在开发激光激活纳米治疗作为细胞消除技术（LANTCET），用于无化学检测和选择性破坏（消除）浅表组织层中的肿瘤细胞，并具有单细胞选择性，从而排除对侧支正常细胞的损伤。LANTCET包括四个主要步骤：（1）局部应用无毒的金纳米颗粒（NP）缀合物，随后由于内吞作用而选择性地形成细胞内NP簇;（2）通过记录NP簇特异性光学散射信号来光学检测具有正常细胞的组织中的肿瘤细胞，（3）选择性机械破坏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，以及（4）通过检测（成像）PTB特异性散射光信号来实时光学引导肿瘤细胞损伤。探测、摧毁和光学制导过程在微秒内完成，而且只用一个装置。LANTCET的有效性、特异性和选择性由细胞光学检测和破坏的NP簇- PT气泡机制提供，其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。组织层中NP簇和PTB的光学监测将引导消融激光脉冲到肿瘤细胞，并帮助确定用于100%损伤肿瘤细胞的最佳激光能量密度和肿瘤破坏的实时光学验证。 公共卫生关系：浅表性癌症如皮肤肿瘤和上呼吸消化道粘膜的早期病变最常通过手术切除治疗。然而，对于皮肤的扩散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，开发更有选择性地靶向肿瘤细胞的替代治疗策略可以提高这些肿瘤类型患者的预后。分子靶向癌症治疗的出现已经显示出显著的前景，最近完成的试验显示，当与表皮生长因子受体（EGFR）结合的单克隆抗体（其由一些癌细胞高度表达）用于治疗上呼吸消化道鳞状细胞癌（SCCHN）时，生存益处。金纳米粒子的几乎同时的发展，可以在原位光学激活，以产生细胞内的光热泡（PTB）表明，耦合肿瘤细胞的分子靶标与纳米粒子激活细胞内的PTB可以作为一种有效的策略，用于检测和治疗癌症在细胞水平。

项目成果

Selective and self-guided micro-ablation of tissue with plasmonic nanobubbles.

• DOI: 10.1016/j.jss.2010.10.039
• 发表时间: 2011-03
• 期刊: The Journal of surgical research
• 作者: Lukianova-Hleb EY;Koneva II;Oginsky AO;La Francesca S;Lapotko DO
• 通讯作者: Lapotko DO

Selective gene transfection of individual cells in vitro with plasmonic nanobubbles.

• DOI: 10.1016/j.jconrel.2011.02.006
• 发表时间: 2011-06-10
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Lukianova-Hleb EY;Samaniego AP;Wen J;Metelitsa LS;Chang CC;Lapotko DO
• 通讯作者: Lapotko DO

Plasmonic nanobubbles as tunable cellular probes for cancer theranostics.

• DOI: 10.3390/cancers3010802
• 发表时间: 2011-02-23
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Lapotko D

Influence of transient environmental photothermal effects on optical scattering by gold nanoparticles.

• DOI: 10.1021/nl9007425
• 发表时间: 2009-05
• 期刊: Nano letters
• 影响因子: 10.8
• 作者: Lukianova-Hleb EY;Lapotko DO
• 通讯作者: Lapotko DO

Plasmonic nanobubbles as transient vapor nanobubbles generated around plasmonic nanoparticles.

• DOI: 10.1021/nn1000222
• 发表时间: 2010-04-27
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Lukianova-Hleb E;Hu Y;Latterini L;Tarpani L;Lee S;Drezek RA;Hafner JH;Lapotko DO
• 通讯作者: Lapotko DO