Novel Cancer Nanotechnology Platforms for Photodynamic Therapy and Imaging

用于光动力治疗和成像的新型癌症纳米技术平台

• 批准号: 7279228
• 负责人: ALLAN R OSEROFF
• 金额: $ 64.67万
• 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/7279228
• 关键词: Acrylamide; Acrylamides; Acute; Animal Model; Animals; Antigens; Area; Avidity; Binding Sites; Biochemical; Biocompatible; Biophotonics; Buffaloes; Cancer Detection; Cardiovascular system; Carrying Capacities; Cell Line; Cells; Ceramics; Characteristics; Charge; Chemicals; Chemistry; Collaborations; Coupling; Data; Depth; Development; Diagnosis; Disease; Doctor of Philosophy; Drug Formulations; Drug Kinetics; Drug or chemical Tissue Distribution; Dyes; Encapsulated; Evaluation; Experimental Designs; Extravasation; Fluorescent Probes; Folic Acid; Generations; Goals; Human Resources; Image; Imaging technology; Immune response; Immunoglobulin Fragments; In Vitro; Individual; Inflammatory; Injectable; Institutes; Label; Lasers; Lead; Leadership; Ligands; Light; Link; Localized; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Methods; Michigan; Modality; Nanotechnology; Numbers; Optics; Peptide Receptor; Peptides; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Photochemotherapy; Photosensitizing Agents; Phototoxicity; Polymers; Positron-Emission Tomography; Preparation; Property; Radiolabeled; Roswell Park Cancer Institute; Silicates; Singlet Oxygen; Site; Solutions; Surface; System; Testing; Therapeutic; Tissues; Toxic effect; Toxicology; Treatment Efficacy; Tumor Tissue; Tumor-Associated Vasculature; Universities; Validation; absorption; base; expectation; functional group; hydrophilicity; image guided therapy; in vivo; nanomaterials; nanoparticle; nanovector; neoplastic cell; novel; optical imaging; photonics; polyacrylamide; pre-clinical; prototype; radiotracer; receptor; receptor binding; research study; self assembly; size; submicron; trafficking; tumor; uptake

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)： 这一跨学科平台开发合作伙伴关系由罗斯威尔公园癌症研究所牵头，布法罗大学激光、光子学和生物光子学研究所以及密歇根大学化学系合作。 总体目标是利用光动力疗法(PDT)和多种成像方式的体内成像和多功能疗法开发有针对性的纳米颗粒(NP)平台。我们展望了多功能NP平台的开发、表征和临床前验证，这种平台提供亲肿瘤的治疗性光敏剂(PS)，这些光敏剂在光照射下才是活性(和有毒的)。NP还携带一种或多种成像剂的有效载荷，从而实现多模式诊断和图像引导治疗。选择性的NP递送来自PS的肿瘤亲和力和/或识别靶细胞的NP表面配体。额外的治疗选择性是由于光对PS的局部激活。 我们推测，生物相容的有机改性硅酸盐溶胶(Ormosil)和聚丙烯酰胺纳米粒(NP)将成为肿瘤治疗和成像(光学、PET、MR)的有效多功能纳米载体。我们的目标是： 1.制备既能治疗肿瘤又能成像的多功能Ormosil和聚合物纳米载体，其中包含具有或不带有额外靶向部分的亲肿瘤PS，以及光学、PET和/或MRI显像剂。 2.对溶液和体外不同的纳米载体进行表征，反复利用目标1中的数据来选择和优化处方。 3.在动物肿瘤系统中检测选定的纳米载体，并将信息迭代应用于目标1和目标2，以进一步完善平台开发。 Allan R.Oseroff，医学博士，PI，将提供总体指导和协调，并将负责细胞和动物模型的评估。Ravi Pandey博士将准备光敏剂和成像有效载荷。Paras Prasad博士(UB)将领导Ormosil平台的开发和光物理表征。拉乌尔·科佩尔曼博士(UM)将领导聚丙烯酰胺平台的开发和光物理表征。