MSKCC -Cornell Center for Translation of Cancer Nanomedicines.

MSKCC - 康奈尔大学癌症纳米药物转化中心。

• 批准号: 8961774
• 负责人: Michelle S Bradbury
• 金额: $ 166.81万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-27 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8961774
• 关键词: Address; Area; Biological; Biological Markers; Cancer Diagnostics; Cancer Patient; Caring; Cell surface; Chemistry; Clinical; Clinical Investigator; Clinical Trials; Clinical Trials Design; Collaborations; Coupled; Coupling; Decision Making; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Disease Progression; Dose-Limiting; Drug Kinetics; Environment; Evaluation; Exhibits; Financial Support; Fluorescence; Fluorescent Probes; Funding; Future; Generations; Genetic Engineering; Geometry; Goals; Grant; Heterogeneity; Human; Hybrids; Image; Image-Guided Surgery; Imaging technology; Immunotherapy; In Vitro; Individual; Industry; Injury; Institution; Investigational Drugs; Label; Lead; Leadership; Malignant Neoplasms; Malignant neoplasm of brain; Melanoma Cell; Memorial Sloan-Kettering Cancer Center; Metastatic Melanoma; Modeling; Molecular; Molecular Genetics; Nanotechnology; New Drug Approvals; Normal tissue morphology; Nucleosome Core Particle; Operative Surgical Procedures; Optics; Outcome; Particle Size; Pathway interactions; Patient Triage; Patients; Pharmaceutical Preparations; Positron-Emission Tomography; Prognostic Marker; Property; Radiation therapy; Relative (related person); Research; Research Personnel; Research Project Grants; Risk; Science; Silicon Dioxide; Site; Solutions; Staging; Structure; Surface; Surgeon; Surgical Management; System; Technology; Therapeutic; Therapeutic Index; Time; Tissues; Toxic effect; Translating; Translational Research; Translations; United States; Universities; Validation; Vision; Water; Work; arm; base; cancer care; cell killing; chemical property; clinical care; clinically relevant; cost effective; design; diagnostic accuracy; experience; human subject; improved; in vivo; inhibitor/antagonist; insight; lymph nodes; melanoma; member; molecular imaging; multidisciplinary; multimodality; nanomaterials; nanomedicine; nanometer; nanoparticle; neoplastic cell; novel; novel diagnostics; novel therapeutics; oncology; outcome forecast; overexpression; particle; particle therapy; prognostic; programs; prospective; public health relevance; receptor; research and development; response; small molecule; tool; tumor

 DESCRIPTION (provided by applicant):: Novel diagnostic and therapeutic tools that can enable earlier and more specific detection, as well as enhance efficacy are critically needed to improve patient outcomes, in particular in melanoma and malignant brain tumors studied in this Center. For example, such tools should enable the operating surgeon to directly visualize tumor margins and metastatic disease spread to lymph nodes, while identifying adjacent vital neurovascular structures. Such structures may be difficult to visualize, thus putting them at risk for injury. Unfortunately, while nanoparticles have a number of desirable features permitting the addition of new functionalities to create a more potent, tumor-directed imaging and/or therapeutic platform, such molecularly targeted, multimodality particles that can improve diagnostic accuracy and/or triage patients to appropriate treatment arms, have been slow to advance to the clinical trial stage. The vision of the MSKCC-Cornell Center for Translation of Cancer Nanomedicines (MC2TCN) is to advance, translate, and disseminate a suite of ultrasmall (<10 nm) multimodality (PET/optical) silica-organic hybrid nanoparticles with tunable size, brightness, and geometry that, as a result of their proven favorable pharmacokinetics, clearance profiles and tumor-to-background ratios in human patients, have the potential to overcome these limitations and dramatically impact the way we diagnose and treat cancer patients. This includes the development and implementation of intraoperative optical detection tools to improve cancer localization, staging, and treatment, as well as the development of optimized therapeutic platforms that enhance delivery and therapeutic index relative to existing technologies. The proposed Center is focused on initial development efforts of diagnostic particle probes, fluorescent core-shell silica nanoparticles referred to as Cornell dots or C dots, which have already received FDA investigational new drug (IND) approvals for first in-human clinical trials. This successful work, for the first time in human patients, has validated the "taret or clear" approach of <10 nm nanoparticles pursued in this Center, opening the door to transformative research and development of new clinically promising classes of nanoparticles and their applications in cancer diagnostics and therapeutics. Transitioning to water-based synthetic approaches proposed here will enable cost-effective creation of novel diagnostic and therapeutic particle platforms with sizes <10 nm. These ultrasmall particle platforms will exhibit high brightness for maximum detection sensitivity by altering particle core composition, lead to particle geometries (rings vs. spheres) with increased surface area for maximizing drug loading capacity, and address the effects of particle size and surface chemistry heterogeneity on PK, clearance profiles and target-to-background ratios - key issues in the use of nanomaterials in nanomedicine. Informed by the encouraging results of the first-in-human clinical trials with first generation multimodal C dots, built on many years of collaborative research between investigators of the proposed multi-institutional, multi-disciplinary team, we envision that the proposed work defined by the framework of this Center and by the use of same-sized particle platforms exhibiting improved and significantly enhanced capabilities has a realistic chance to change the paradigm of cancer care applications pursued herein.

 描述（由申请人提供）：：迫切需要能够实现更早和更特异性检测并提高疗效的新型诊断和治疗工具，以改善患者结局，特别是在本中心研究的黑色素瘤和恶性脑肿瘤中。例如，这种工具应该使手术外科医生能够直接可视化肿瘤边缘和转移性疾病扩散到淋巴结，同时识别相邻的重要神经血管结构。这些结构可能难以可视化，从而使它们处于受伤的风险中。不幸的是，虽然纳米颗粒具有许多期望的特征，允许添加新的功能以创建更有效的肿瘤定向成像和/或治疗平台，但是可以提高诊断准确性和/或将患者分诊到适当的治疗组的这种分子靶向的多模态颗粒在进入临床试验阶段方面进展缓慢。MSKCC-Cornell癌症纳米医学翻译中心（MC 2 TCN）的愿景是推进，翻译和传播一套超小型（<10 nm）多模态具有可调尺寸、亮度和几何形状的（PET/光学）二氧化硅-有机杂化纳米颗粒，由于其在人类患者中被证明的有利的药代动力学、清除曲线和肿瘤与背景比，有可能克服这些局限性，并极大地影响我们诊断和治疗癌症患者的方式。这包括术中光学检测工具的开发和实施，以改善癌症定位，分期和治疗，以及优化治疗平台的开发，相对于现有技术，增强递送和治疗指数。拟议中的中心的重点是诊断粒子探针，荧光核壳二氧化硅纳米粒子称为康奈尔点或C点， 这些药物已经获得FDA研究新药（IND）的批准，用于首次人体临床试验。这一成功的工作首次在人类患者中验证了该中心追求的<10 nm纳米颗粒的“taret or clear”方法，为新的临床有前途的纳米颗粒及其在癌症诊断和治疗中的应用的变革性研究和开发打开了大门。过渡到本文提出的水基合成方法将能够经济有效地创建尺寸<10纳米的新型诊断和治疗颗粒平台。这些超小颗粒平台将通过改变颗粒核心组成来表现出高亮度以获得最大检测灵敏度，产生具有增加的表面积的颗粒几何形状（环与球）以最大化药物负载能力，并解决粒度和表面化学异质性对PK、清除率曲线和靶-背景比的影响-纳米医学中使用纳米材料的关键问题。基于第一代多模式C点的首次人体临床试验的令人鼓舞的结果，建立在拟议的多机构，多学科团队的研究人员之间多年的合作研究基础上，我们设想，由该中心的框架定义的拟议工作，并通过使用相同的-显示出改进的和显著增强的能力的尺寸的颗粒平台具有改变本文所追求的癌症护理应用的范例的现实机会。