Near Infrared Semiconductor Nanocrystal for Imaging Guided Surgery

描述（申请人提供）：纳米材料和纳米制造实验室计划公告号：题目：用于成像引导手术的近红外半导体纳米晶体主要研究者：Tiecheng Qiao摘要：黑色素瘤患者脑转移的发生率在10%到40%之间，在尸检系列中甚至更高。IV期患者的生存率通常以月为单位。手术通常建议单脑转移患者控制或可控的全身性疾病。在可能的情况下，应进行全面和积极的手术切除，并进行术后放射治疗。然而，在传统的白光照明下，外科医生区分残余肿瘤和周围脑组织的能力有时会限制完全切除（即阴性切缘）的能力。为了解决这一技术难题，该第一阶段项目将开发一种新型的近红外纳米颗粒（NIR-NP），用于成像引导手术（ICG）应用。这种材料目前还没有商业化，将为外科医生提供一种易于使用的手术导航成像剂，具有精确和实时的反馈，总体上改善癌症患者的临床结果。我们将选择一种肿瘤靶向肽，它将附着在近红外纳米颗粒的表面。以荷瘤小鼠为模型，观察近红外纳米粒子在肿瘤部位的良好蓄积。使用近红外纳米颗粒引导切除小鼠肿瘤与简单的视觉切除的优势将被证明。成功的标准包括以下要求：近红外纳米粒子必须是易于分散的生物良性溶液，如磷酸盐缓冲盐水溶液（PBS），无团聚。近红外纳米颗粒必须具有良好的生物分布和体内清除特性。近红外纳米颗粒必须满足或超过临床要求。我们将通过一系列体外实验来评估NIR-NP的细胞毒性和生物相容性。最终，我们将在皮下接种B16-BL6黑色素瘤的小鼠模型中证明在IGS中使用NIR-NP的可行性和益处，而不是传统的视觉手术。公共卫生相关性：美国每年约有150万人被诊断患有癌症；今年在美国新诊断的150万癌症病例中，有一半将通过切除手术治疗。与肿瘤相关的外科手术相关的一个常见问题是外科医生在手术前难以看到肿瘤边缘并在手术中完成癌变组织的切除。据估计，肿瘤切除手术后的肿瘤复发率可高达20-30%，并且随后未切除的肿瘤生长转移导致进一步的临床并发症。该项目的目标是开发一种使用近红外纳米颗粒的成像引导手术系统，使外科医生能够最大限度地切除肿瘤，同时将肿瘤周围正常组织的损伤降到最低。近红外成像有可能提高术中对恶性肿瘤患者的检测，手术切除是必须的。预计更低的成本和更高的分辨率将允许更完整的肿瘤切除，更准确的活检，更快的手术，更好的患者结果，更低的患者成本和发病率。

DESCRIPTION (provided by applicant): Nanomaterials and Nanofabrication Laboratories Program Announcement No. PA-08-050 (NN-Labs, LLC) Title: Near Infrared Semiconductor Nanocrystal for Imaging Guided Surgery Principal Investigator: Tiecheng Qiao Summary The incidence of brain metastasis in patients with melanoma ranges from 10% to 40% and is even higher in autopsy series. Survival rate for patients with stage IV disease is typically measured in months. Surgery is usually recommended for single brain metastases in patients with controlled or controllable systemic disease. A complete and aggressive surgical resection should be performed whenever possible followed by post-operative radiation. However, the ability to achieve complete resection (i.e., negative margin) is sometimes limited by the surgeon's ability to distinguish residual tumor from surrounding brain tissue under conventional white-light illumination. To address this technical difficulty, this Phase I project will develop a novel class of near infrared nanoparticles (NIR-NP) for imaging guide surgery (ICG) applications. Such materials are not commercially available today and will provide surgeons an ease of use surgical navigation imaging agent with precision and real time feedback, and overall, improve clinical outcome for cancer patients. We will select a tumor targeting peptide that will be attached to the surface of NIR nanoparticles. Tumor bearing mice will be used as a model to show the preferably accumulation of NIR nanoparticles on tumor site. The advantage of using a NIR nanoparticles guided resection of tumor in mice versus simple visual resection will be demonstrated. Criteria for success involve the following requirements: 1. The NIR nanoparticles must be readily dispersible biological benign solution, such as phosphate buffer saline solution (PBS), without agglomeration, 2. The NIR nanoparticles must possess good biodistribution and body clearance profile, 3. The NIR nanoparticle must meet, or exceed, clinical requirements. We will evaluate the cytotoxicity and biocompatibility of our NIR-NP through a series of in vitro assays. Ultimately, we will demonstrate the feasibility and benefit of using NIR-NP in IGS over conventional visual surgery in mice model with subcutaneously inoculated B16-BL6 melanoma. 1 PUBLIC HEALTH RELEVANCE: Approximately 1.5 million people in the US are diagnosed with cancer annually; and half of the 1.5 million new cancer cases diagnosed in the U.S. this year will be treated with excision surgery. One common problem associated with tumor-related surgical procedures is the difficulty for surgeons to visualize the tumor margin before the operation and to complete the excision of cancerous tissue during surgery. It is estimated that tumor reoccurrence rate could be as high as 20-30% after tumor-excision surgical procedures, and that the subsequent metastasis of unexcised cancerous growth leads to further clinical complications. The goal of this program is to develop an imaging guided surgery system using near infrared nanoparticles that would allow surgeons to maximizing tumor removal with minimal peri-tumoral damage to surrounding normal tissue. Near infrared imaging has the potential to improve the intraoperative detection of patients with malignant tumor that surgical resection is a must procedure. It is anticipated that the reduced costs and higher resolutions will permit more complete tumor resections, more accurate biopsies, and faster procedures with better patient outcomes and lower patient cost and morbidity.