Engineering Multifunctional Nanoparticles

工程多功能纳米粒子

基本信息

批准号：
7911031
负责人：
SANGEETA N. BHATIA
金额：
$ 56.9万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7911031
关键词：
Address Adsorption Animal Cancer Model Apoptotic Area Artificial nanoparticles Atomic Force Microscopy Binding Biodistribution Biological Assay Biological Process Biomedical Engineering Biotin Blood Blood Platelets Blood Vessels Cell surface Chemistry Cleaved cell Clinical Collaborations Coupled Development Dextrans Diagnostic Doctor of Philosophy Dose Doxorubicin Drug Delivery Systems Drug Formulations Early Diagnosis Electromagnetic Energy Electromagnetic Fields Electromagnetics Electron Microscopy Engineering Explosion Fluorescence Funding Gelatinase A Generations Goals Health Heating Histologic Home environment Homing Human Image In Vitro Injury Institutes Laboratories Lead Left Liver Lymphatic Magnetic Resonance Imaging Magnetism Malignant Neoplasms Medical Methods Modeling Mus Nanotechnology Opsonin Particulate Peptide Hydrolases Peptides Performance Phage Display Pharmaceutical Preparations Plasma Proteins Polyethylene Glycols Principal Investigator Process Property Publications Quantum Dots Rage Research Personnel Resolution Role Sailor Science Scientist Serum Proteins Site Solutions Spleen Squid Stream Students Supervision Surface System Technology Therapeutic Time Tissues Translations Treatment Protocols Tumor Biology Tumor Burden Ultrasonics Weight X ray diffraction analysis X-Ray Diffraction Xenograft procedure aqueous base biomaterial compatibility cancer therapy crosslink design dextran effective therapy experience improved in vivo interstitial iron oxide light scattering malignant breast neoplasm member mouse model multidisciplinary nanobiotechnology nanodevice nanomaterials nanoparticle nanostructured neutravidin novel novel strategies particle programs self assembly sensor targeted delivery tool transduction efficiency tumor tumor xenograft

项目摘要

DESCRIPTION (provided by applicant): Recently, there has been an explosion of new nanomaterials with the potential to impact both medical science and human health. Translation of these discoveries to early diagnosis and effective treatment of malignancy are key clinical goals set forth by the NCI. Accordingly, this BRP is focused on the engineering of multifunctional nanoparticles that will exploit biological processes to guide the targeting, self-assembly, and remote actuation of nanoparticles to treat tumors in mouse models of cancer. The multidisciplinary team includes members with complementary expertise in biomedical engineering (Dr. Sangeeta Bhatia, MIT), chemistry and materials science (Dr. Michael Sailor, UCSD), and tumor biology (Dr. Erkki Ruoslahti, Burnham Institute) with a track record of collaborative invention, student supervision, funding, and publication. Motivated by the inefficiency of current targeting technologies, we sought to design nanoparticles that mimic the targeted accumulation of platelets at specific sites of vascular injury. We further sought to exploit the emergent properties of ensembles of nanomaterials to improve capabilities in imaging and drug delivery upon accumulation at tumor sites. Accordingly, the multifunctional nanoparticles will be based on dextran-coated iron oxide nanoparticles engineered to: (1) target tumors via phage-display derived peptides, (2) self-assemble in tumors via protease activation and plasma protein-aided trapping, (3) be detected using shifts in T2 relaxivity by MRI, and (4) deliver drugs via remote actuation using electromagnetic fields. The effort will be divided into three areas representing the expertise of the participating laboratories. The drug-loaded superparamagnetic materials will be developed and characterized by Dr. Sailor's group. Dr. Ruoslahti provides animal models of cancer, targeting expertise, and methods for identification of novel peptides via phage display. Dr. Bhatia's expertise lies in micro- and nanotechnology tools to probe cellular interfaces. Her role will be to engineer nanoparticles that can undergo triggered self-assembly, remote actuation, and in vivo imaging. The combination of these technologies and investigators is expected to lead to the development of a new generation of nanodevices that will significantly advance both medical science and treatment of cancer.

描述（由申请人提供）：最近，新的纳米材料爆炸，有可能影响医学和人类健康。这些发现的转换为早期诊断和有效治疗恶性肿瘤是NCI提出的关键临床目标。因此，该BRP的重点是多功能纳米颗粒的工程，这些纳米颗粒将利用生物学过程来指导纳米颗粒的靶向，自组装和远程驱动以治疗癌症小鼠模型中的肿瘤。多学科团队包括具有生物医学工程专业知识（MIT的Sangeeta Bhatia博士），化学和材料科学（Michael Sailor，UCSD）和肿瘤生物学（Erkki Ruoslahti，Burnham Institute）以及协作，学生监督，学生监督，学生的往绩记录的成员。由于当前靶向技术的效率低下，我们试图设计模仿血小板在血管损伤特定部位的靶向积累的纳米颗粒。我们进一步寻求利用纳米材料集合的新兴特性，以提高肿瘤部位积累后的成像和药物输送能力。因此，多功能纳米颗粒将基于葡萄糖涂层的氧化铁纳米颗粒，该纳米颗粒设计为：（1）通过噬菌体 - 播种型肽靶向肿瘤，（2）通过蛋白酶激活和血浆蛋白蛋白蛋白质诱捕来检测蛋白酶激活和（3）在肿瘤中进行自我组装，（3）使用MRI进行了传播（3），（3）用于（3）字段。这项工作将分为代表参与实验室的专业知识的三个领域。载有药物的超级磁材料将由Sailor's Group博士组开发和特征。 Ruoslahti博士提供了癌症的动物模型，靶向专业知识以及通过噬菌体显示鉴定新肽的方法。 Bhatia博士的专业知识在于微技术和纳米技术工具探测细胞界面。她的角色是工程师纳米颗粒，这些纳米颗粒可以受到触发的自组装，远程驱动和体内成像。预计这些技术和研究人员的结合将导致新一代的纳米版本的发展，这些纳米版将大大推动医学科学和癌症的治疗。