Nanoparticle contrast agents for earlier breast cancer detection

用于早期乳腺癌检测的纳米粒子造影剂

基本信息

批准号：
9925060
负责人：
David Peter Cormode
金额：
$ 52.44万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9925060
关键词：
Address Affect Behavior Biological Blood Blood Circulation Body Weights and Measures Breast Breast Cancer Detection Breast Cancer Early Detection Breast Cancer Model Breast Cancer Risk Factor Breast Cancer Treatment Caliber Claustrophobias Clinical Clinical Chemistry Clinical Data Contrast Media Data Detection Digital Mammography Disease Drug Kinetics Early Diagnosis Effectiveness Elements Encapsulated Equipment Excretory function Formulation Gold High Risk Woman Histology Hour Hypersensitivity Image In Vitro Inductively Coupled Plasma Mass Spectrometry Iodine Kidney Kidney Failure Libraries Magnetic Resonance Imaging Malignant Neoplasms Mammographic screening Mammography Methods Minor Nanosphere Nanostructures Organ Patients Polymers Population Procedures Property Publishing Roentgen Rays Safety Scanning Screening procedure Silver Solubility Specificity Structure System Techniques Testing Time Toxic effect Transgenic Model Translations Variant Woman anti-cancer base biodegradable polymer biomaterial compatibility cancer imaging cancer type comparative contrast enhanced cost cost effective design flexibility high risk high risk population hydrophilicity imaging potential improved in vitro Assay in vivo malignant breast neoplasm mortality nanocrystal nanomaterials nanoparticle novel polyphosphazene prevent public health relevance screening screening program silver sulfide small molecule tool tumor

Address Affect Behavior Biological Blood Blood Circulation Body Weights and Measures Breast Breast Cancer Detection Breast Cancer Early Detection Breast Cancer Model Breast Cancer Risk Factor Breast Cancer Treatment Caliber Claustrophobias Clinical Clinical Chemistry Clinical Data Contrast Media Data Detection Digital Mammography Disease Drug Kinetics Early Diagnosis Effectiveness Elements Encapsulated Equipment Excretory function Formulation Gold High Risk Woman Histology Hour Hypersensitivity Image In Vitro Inductively Coupled Plasma Mass Spectrometry Iodine Kidney Kidney Failure Libraries Magnetic Resonance Imaging Malignant Neoplasms Mammographic screening Mammography Methods Minor Nanosphere Nanostructures Organ Patients Polymers Population Procedures Property Publishing Roentgen Rays Safety Scanning Screening procedure Silver Solubility Specificity Structure System Techniques Testing Time Toxic effect Transgenic Model Translations Variant Woman anti-cancer base biodegradable polymer biomaterial compatibility cancer imaging cancer type comparative contrast enhanced cost cost effective design flexibility high risk high risk population hydrophilicity imaging potential improved in vitro Assay in vivo malignant breast neoplasm mortality nanocrystal nanomaterials nanoparticle novel polyphosphazene prevent public health relevance screening screening program silver sulfide small molecule tool tumor

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项目摘要

PROJECT SUMMARY Breast cancer is by far the most common type of cancer and is the second most deadly cancer in women. Breast cancer mammography screening programs for early detection are widespread. Mammography screening reduces mortality from breast cancer and is cost-effective. However, it has emerged that mammography is not very effective in women with dense breasts (about 10% of women), with sensitivity of 30- 60%. Moreover, independent of the lower chance of tumor detection, women with dense breasts are at a higher risk of breast cancer. Therefore to reduce mortality from breast cancer in this population, better screening techniques are needed. Dual-energy mammography has recently emerged as a technique that is highly sensitive and specific for detecting cancer in women with dense breasts. A contrast agent for dual-energy mammography that can identify tumors would be highly beneficial in women with dense breasts, as well as in selected high-risk populations. Currently available iodine-based contrast agents have poor pharmacokinetics, low tumor accumulation and are contraindicated in many patients. While other techniques such as contrast-enhanced MRI can be used for screening women with dense breasts, the high costs and practical obstacles prevent the use of those techniques. We herein propose to develop novel, biodegradable silver-based nanoparticles (SBNP) to allow safe detection of tumors in patients at higher risk of breast cancer. We have found that silver is an element that produces excellent contrast in dual-energy mammography a new variation of mammography where two images are acquired at different x-ray energies. We have found methods that make the nanoparticles stable and biocompatible. We have chosen a comparatively simple, yet flexible nanoparticle design in order to improve the likelihood of translation. The nanoparticles should quickly accumulate in tumors, rendering them conspicuous on mammography, before gradually breaking down into their components for renal excretion. This proposal addresses a key challenge in the use of nanoparticles in cancer: excretion. As part of this proposal we will develop a biodegradable carrier system that can deliver small, highly hydrophilic nanoparticles to tumors, before breakdown and renal excretion. This carrier system could have a broad impact, since it could be applied to numerous different nanoparticle types and anti-cancer approaches.

项目摘要乳腺癌是迄今为止最常见的癌症类型，是女性第二大致命癌。乳腺癌乳腺X线摄影筛查计划的早期检测计划很普遍。乳房X线摄影筛查可降低乳腺癌的死亡率，并且具有成本效益。但是，它已经出现了乳房X线摄影在乳房密集的女性（约10％的女性）中不是很有效，灵敏度为30- 60％。此外，与肿瘤检测的较低机会无关，乳房密集的女性处于乳腺癌的风险更高。因此，为了降低该人群中乳腺癌的死亡率，更好需要筛选技术。双能乳腺X线摄影最近已成为一种高度敏感且特异的技术检测乳房密集的女性的癌症。双能乳腺X线摄影的对比剂，可以鉴定肿瘤对乳房密集的女性以及选定的高风险是非常有益的人群。目前可用的基于碘的对比剂的药代动力学较差，低肿瘤积累，许多患者禁忌。而其他技术（例如对比度增强） MRI可用于筛查乳房密集的妇女，高成本和实际障碍阻止使用这些技术。我们在这里建议开发新颖的可生物降解银纳米颗粒（SBNP）以允许安全检测患有乳腺癌风险较高的患者肿瘤。我们发现银是产生的元素双能乳腺X线摄影中的出色对比是乳房X线摄影的新变化，其中有两个图像在不同的X射线能量中获得。我们发现了使纳米颗粒稳定的方法生物相容性。我们选择了一种相对简单但灵活的纳米颗粒设计，以改进翻译的可能性。纳米颗粒应迅速积聚在肿瘤中，使其呈现在乳房X线摄影显着，然后逐渐分解成其肾脏排泄的成分。这提案解决了在癌症中使用纳米颗粒的主要挑战：排泄。作为本提案的一部分我们将开发一个可生物降解的载体系统，该系统可以将小的，高度亲水的纳米颗粒传递到肿瘤，分解和肾脏排泄之前。该运营商系统可能会产生广泛的影响，因为它可以应用于多种不同的纳米颗粒类型和抗癌方法。