Novel Cancer Nanotechnology Platforms for Photodynamics

描述（由申请人提供）： 这个跨学科平台开发伙伴关系由罗斯韦尔公园癌症研究所领导，与布法罗大学激光、光子学和生物光子学研究所以及密歇根大学化学系合作。 总体目标是开发靶向纳米颗粒（NP）平台，利用光动力学疗法（PDT）和多种成像方式在体内成像和多功能治疗。 我们设想开发，表征和临床前验证的多功能NP平台，提供肿瘤亲和性，治疗性光敏剂（PS），只有在光照射时才有活性（和毒性）。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NP递送来自PS的肿瘤亲合力和/或来自识别靶细胞的NP表面配体。额外的治疗选择性是由于光对PS的局部激活。 我们假设生物相容性有机改性硅酸盐溶胶（Ormosil）和聚丙烯酰胺NP将是有效的多功能纳米载体用于肿瘤治疗和成像（光学，PET，MR）。我们的目标是： 1.制备能够进行肿瘤治疗和成像的多功能Ormosil和聚合物纳米载体，其含有具有或不具有额外靶向部分的亲肿瘤PS，以及光学、PET和/或MRI成像剂。 2.表征溶液中和体外的不同纳米载体，并反复利用目标1中的数据来选择和优化制剂。 3.在动物肿瘤系统中检查选定的纳米载体，并将信息反复应用于目标1和2，以进一步完善平台开发。 Allan R.主要研究者Oseroff，MD，PhD将提供总体指导和协调，并负责细胞和动物模型评价。 Ravi Pandey博士（RPCI）将准备光敏剂和成像有效载荷。 Paras Prasad博士（UB）将领导Ormosil平台的开发和地球物理表征。 拉乌尔Kopelman博士（UM）将领导聚丙烯酰胺平台的开发和物理表征。

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.