Novel Cancer Nanotechnology Platforms for Photodynamic *

新型癌症光动力纳米技术平台 *

• 批准号: 7127659
• 负责人: ALLAN R OSEROFF
• 金额: $ 64.97万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127659
• 关键词: antineoplastics; athymic mouse; bioimaging /biomedical imaging; cell line; drug delivery systems; folacin; image guided surgery /therapy; intracellular transport; magnetic resonance imaging; nanotechnology; neoplasm /cancer photoradiation therapy; particle; pharmacokinetics; photosensitizing agents; polyacrylamide; positron emission tomography; silicates; technology /technique development

DESCRIPTION (provided by applicant): This interdisciplinary platform development partnership is led by Roswell Park Cancer Institute, with the collaboration of the Institute for Lasers, Photonics and Biophotonics at the University of Buffalo, and the Department of Chemistry at the University of Michigan. The overall goal is to develop targeted nanoparticle (NP) platforms utilizing photodynamic therapy (PDT) and multiple imaging modalities in vivo imaging and multifunctional therapeutics. We envision development, characterization and preclinical validation of multifunctional NP platforms that deliver tumor-avid, therapeutic photosensitizers (PS) that only are active (and toxic) when illuminated by light. The NP also carries a payload of one or more imaging agents, enabling both multimodal diagnosis and image-guided therapy. Selective NP delivery comes from the tumor avidity of the PS and/or from NP surface ligands that recognize targeted cells. Additional therapeutic selectivity is due to local activation of the PS by light. We hypothesize that biocompatible organically modified silicate sol (Ormosil) and polyacrylamide NP will be effective multi-functional nanovectors for tumor therapy and imaging (optical, PET, MR). Our aims are: 1. To prepare multifunctional Ormosil and polymeric nanovectors capable of both tumor therapy and imaging, which contain tumor-avid PS with or without additional targeting moieties, as well as optical, PET, and/or MRI imaging agents. 2. To characterize the different nanovectors in solution and in vitro and iteratively utilize the data within Aim 1 to select and optimize formulations. 3. To examine selected nanovectors in animal tumor systems and iteratively apply the information to Aims 1 and 2 to further refine the platform development. Allan R. Oseroff, MD, PhD, the PI, will provide overall direction and coordination and will be responsible for the cellular and animal model evaluations. Ravi Pandey, PhD (RPCI), will prepare the photosensitizers and the imaging payloads. Paras Prasad, PhD (UB), will lead development and photophysical characterization of the Ormosil platform. Raoul Kopelman, PhD (UM), will lead development and photophysical characterization the polyacrylamide platform.

描述（由申请人提供）： 这种跨学科的平台发展合作伙伴关系由罗斯威尔公园癌症研究所（Roswell Park Cancer Institute）领导，布法罗大学的激光，光子学和生物光谱学研究所以及密歇根大学化学系的合作。 总体目标是开发利用光动力疗法（PDT）和多种成像方式的靶向纳米颗粒（NP）平台，并在体内成像和多功能疗法中使用。 我们设想对多功能NP平台的开发，表征和临床前验证，这些平台可提供避免肿瘤的，治疗的光敏剂（PS），这些光敏剂（PS）在光线照明时仅活跃（和有毒）。 NP还携带一种或多种成像剂的有效载荷，从而实现了多模式诊断和图像引导的治疗。选择性NP的递送来自PS和/或NP表面配体的肿瘤亲和力。额外的治疗选择性是由于光线局部激活PS。 我们假设生物相容性的有机修饰的硅酸盐溶胶（Ormosil）和聚丙烯酰胺NP将是用于肿瘤疗法和成像的有效多功能纳米旋转器（光学，PET，MR）。我们的目标是： 1。准备多功能的Ormosil和聚合物纳米腔，具有肿瘤疗法和成像，其中包含带有或不带有其他靶向部分的肿瘤PS，以及光学，PET和/或MRI成像剂。 2。在溶液和体外和迭代中使用AIM 1中的数据来选择和优化配方中的数据。 3。检查动物肿瘤系统中选定的纳米分离器，并迭代地将信息应用于目标1和2，以进一步完善平台开发。 Allan R. Oseroff，医学博士，博士，PI，将提供整体方向和协调，并将负责细胞和动物模型评估。 Ravi Pandey博士（RPCI）将准备光敏剂和成像有效载荷。 Paras Prasad，PhD（UB）将领导Ormosil平台的发育和光物理表征。 Raoul Kopelman博士（UM）将领导发育和光物理表征聚丙烯酰胺平台。