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: 9324181
• 负责人: Michelle S Bradbury
• 金额: $ 160.41万
• 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/9324181
• 关键词: Address; Area; Biological; Biological Markers; Cancer Diagnostics; Cancer Patient; Cell surface; Chemicals; Chemistry; Clinical; Clinical Investigator; Clinical Trials; Clinical Trials Design; Collaborations; Coupled; Coupling; Decision Making; Detection; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Disease Progression; Dose-Limiting; Drug Approval; Drug Kinetics; Environment; Evaluation; Exhibits; Financial Support; Fluorescence; Funding; Future; Generations; Genetic; 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; Localized Malignant Neoplasm; Malignant Neoplasms; Malignant neoplasm of brain; Melanoma Cell; Memorial Sloan-Kettering Cancer Center; Metastatic Melanoma; Modeling; Molecular; Molecular Target; Nanotechnology; Normal tissue morphology; Nucleosome Core Particle; Operative Surgical Procedures; Optics; Particle Size; Pathway interactions; Patient Triage; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Positron-Emission Tomography; Prognostic Marker; Property; Radiation therapy; Research; Research Personnel; Research Project Grants; Risk; Science; Silicon Dioxide; Site; Staging; Structure; Surface; Surgeon; Surgical Management; System; Technology; Therapeutic; Therapeutic Index; Time; Tissues; Toxic effect; Translating; Translations; United States; Universities; Validation; Vision; Water; Work; arm; base; cancer care; cell killing; clinical care; clinically relevant; cost effective; design; diagnostic accuracy; experience; handheld equipment; human subject; improved; in vivo; inhibitor/antagonist; insight; lymph nodes; melanoma; member; molecular imaging; multidisciplinary; multimodality; multiplex detection; nanomaterials; nanomedicine; nanometer; nanoparticle; neoplastic cell; neurovascular; novel; novel diagnostics; novel therapeutics; oncology; outcome forecast; overexpression; particle; particle therapy; personalized care; predictive marker; prospective; public health relevance; receptor; research and development; response; response biomarker; small molecule inhibitor; standard of care; tool; translational research program; 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、更具体的检测并提高疗效的新型诊断和治疗工具，以改善患者的治疗结果，特别是在本中心研究的黑色素瘤和恶性脑肿瘤中。 ，这些工具应该使手术外科医生能够直接观察肿瘤边缘和扩散到淋巴结的转移性疾病，同时识别邻近的重要神经血管结构可能很难观察到，从而使它们面临受伤的风险。数字允许添加新功能以创建更有效的肿瘤导向成像和/或治疗平台的理想特征，这种可以提高诊断准确性和/或将患者分流至适当治疗组的分子靶向多模态颗粒的开发进展缓慢。 MSKCC-康奈尔癌症纳米医学转化中心 (MC2TCN) 的愿景是推进、转化和传播一套超小型（<10 nm）多模态技术。 （PET/光学）二氧化硅-有机杂化纳米颗粒具有可调节的尺寸、亮度和几何形状，由于其在人类患者中被证明具有良好的药代动力学、清除特性和肿瘤背景比，因此有可能克服这些限制，这极大地影响了我们诊断和治疗癌症患者的方式，包括开发和实施术中光学检测工具以改善癌症定位、分期和治疗，以及开发优化的治疗平台以相对于现有技术提高递送和治疗指数。拟议的中心重点关注诊断粒子探针、荧光核壳二氧化硅纳米粒子（称为康奈尔点或 C 点）的初步开发工作。 该药物已获得 FDA 首次人体临床试验的研究性新药 (IND) 批准，这是首次在人类患者中进行的成功工作，验证了该中心所追求的 <10 nm 纳米粒子的“塔雷特或透明”方法。 ，为具有临床前景的新型纳米粒子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，过渡到此处提出的水基合成方法将能够经济高效地创建具有尺寸的新型诊断和治疗粒子平台。 <10 nm。这些超小颗粒平台将通过改变颗粒核心成分表现出高亮度，实现最大检测灵敏度，形成具有增加表面积的颗粒几何形状（环形与球体），以最大限度地提高药物负载能力，并解决颗粒尺寸和粒径的影响。 PK、清除曲线和目标与背景比率的表面化学异质性 - 在纳米医学中使用纳米材料的关键问题 得益于第一代多峰 C 的首次人体临床试验的令人鼓舞的结果。点，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的基础上，我们预计，由该中心的框架和使用相同大小的粒子平台定义的拟议工作将表现出改进和显着的效果增强的能力有一个现实的机会来改变本文所追求的癌症护理应用的范式。