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（由适用提供）::新颖的诊断和治疗工具，这些工具可以促进早期，更具体的检测以及提高效率，以改善患者预后，特别是在该中心的黑色素瘤和恶性脑肿瘤中。例如，这种工具应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，同时鉴定邻近的重要神经血管结构。这样的结构可能很难形象化，从而使它们处于受伤的风险。不幸的是，尽管纳米颗粒具有许多理想的特征，允许添加新的功能来创建更多的潜在，肿瘤导向的成像和/或治疗平台，但这种具有分子靶向的，多模式的颗粒可以提高诊断精度，并且可以改善适当的治疗臂，从而缓慢地提高到临床试验阶段。 MSKCC纳米药物翻译中心（MC2TCN）的愿景是推进，翻译和传播一套超毛剂（<10 nm）多模式（PET/PET/光学）硅胶杂交纳米粒子，具有可调节的大小，亮度，亮度，亮度，并具有良好的示例，并具有可调性，并具有可调性，并具有可调性，并具有良好的范围，并具有可调状的效果，并具有良好的示例。人类患者的比率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，以增强相对于现有技术的交付和治疗指数。拟议的中心侧重于诊断粒子问题的初步开发工作，荧光芯壳二氧化硅纳米颗粒称为康奈尔点或C点， 这项成功的工作在人类患者中首次验证了该中心追求的<10 nm纳米颗粒的“ taret或清晰”方法，为新的临床纳米颗粒及其在癌症诊断和治疗中的应用开放了转化性研究和开发。在此提出的过渡到水基合成方法将使尺寸<10 nm的新型诊断和治疗粒子平台创建具有成本效益的创建。这些超级粒子平台将通过改变粒子核心组成，导致粒子几何形状（环与球形），表面积增加，以提高表面积，以最大程度地驱动载荷能力，并解决粒径和表面化学异质性对PK的影响，并解决了PK的效果，从而提高了粒子的几何形状（环与球形），从而表现出较高的亮度，从而最大程度地检测灵敏度。通过与第一代多式联运C点的令人鼓舞的结果所吸引的结果，这是建立在多年的合作研究的基础上在这里追捕。