Near Infrared Semiconductor Nanocrystal for Imaging Guided Surgery

描述（由申请人提供）：纳米材料和纳米纤维实验室计划公告编号PA-08-050（NN-Labs，LLC）标题：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总结黑色素瘤患者脑转移的发生率范围为10%至40%，在尸检系列中甚至更高。IV期疾病患者的生存率通常以月为单位测量。手术通常被推荐为控制或可控的全身性疾病患者的单一脑转移瘤。应尽可能进行完整和积极的手术切除，然后进行术后放疗。然而，实现完全切除的能力（即，阴性边缘）有时受限于外科医生在常规白光照明下区分残余肿瘤与周围脑组织的能力。为了解决这一技术难题，第一阶段项目将开发一种新型的近红外纳米粒子（NIR-NP），用于成像引导手术（ICG）应用。这样的材料目前还没有商业上可获得的，并且将为外科医生提供易于使用的具有精确和真实的时间反馈的手术导航成像剂，并且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NIR纳米颗粒的表面。荷瘤小鼠将用作模型以显示NIR纳米颗粒在肿瘤部位上的优选积累。将证明使用NIR纳米颗粒引导的小鼠肿瘤切除相对于简单的视觉切除的优势。成功的标准包括以下要求：1。NIR纳米颗粒必须是易于分散的生物良性溶液，例如磷酸盐缓冲盐水溶液（PBS），而没有团聚。NIR纳米颗粒必须具有良好的生物分布和身体清除率。NIR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试验评估我们的NIR-NP的细胞毒性和生物相容性。最终，我们将证明在皮下接种B16-BL 6黑色素瘤的小鼠模型中，在IGS中使用NIR-NP优于常规视觉手术的可行性和益处。1.公共卫生相关性：美国每年约有150万人被诊断出患有癌症;今年美国诊断出的150万新癌症病例中有一半将接受切除手术治疗。与肿瘤相关的外科手术相关的一个常见问题是外科医生难以在手术前观察肿瘤边缘并在手术期间完成癌组织的切除。据估计，肿瘤切除手术后肿瘤复发率可高达20-30%，并且未切除的癌生长的后续转移导致进一步的临床并发症。该计划的目标是开发一种使用近红外纳米粒子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，同时对周围正常组织的损伤最小。近红外成像有可能提高恶性肿瘤患者的术中检测，手术切除是必须的程序。预计降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，更快的程序，更好的患者结果和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.