Engineering Multifunctional Nanoparticles

描述（由申请人提供）：最近，有可能影响医学科学和人类健康的新型纳米材料出现了爆炸式增长。将这些发现转化为恶性肿瘤的早期诊断和有效治疗是NCI提出的关键临床目标。因此，本BRP专注于多功能纳米颗粒的工程设计，该工程将利用生物过程来指导纳米颗粒的靶向、自组装和远程驱动，以治疗小鼠癌症模型中的肿瘤。多学科团队的成员在生物医学工程（麻省理工学院的Sangeeta Bhatia博士）、化学和材料科学（加州大学圣地亚哥分校的Michael Sailor博士）和肿瘤生物学（伯纳姆研究所的Erkki Ruoslahti博士）方面具有互补的专业知识，并在合作发明、学生监督、资助和发表方面有着良好的记录。由于目前靶向技术的低效率，我们试图设计纳米颗粒来模拟血小板在血管损伤的特定部位的靶向积累。我们进一步寻求利用纳米材料集合体的涌现特性，以提高肿瘤部位积累时的成像和药物递送能力。因此，多功能纳米颗粒将基于葡聚糖包覆的氧化铁纳米颗粒，其设计目的是：(1)通过噬菌体展示衍生肽靶向肿瘤，(2)通过蛋白酶激活和血浆蛋白辅助捕获在肿瘤中自组装，(3)通过MRI的T2弛性位移检测，以及(4)通过电磁场远程驱动递送药物。这项工作将分为三个领域，代表各参与实验室的专门知识。这种载药超顺磁材料将由赛勒博士的团队开发和表征。Ruoslahti博士提供癌症动物模型，靶向专业知识，以及通过噬菌体展示识别新肽的方法。巴蒂亚博士的专长在于微型和纳米技术工具来探测细胞界面。她的角色将是设计纳米粒子，可以进行触发自组装，远程驱动和体内成像。这些技术和研究人员的结合有望导致新一代纳米设备的发展，这将大大推进医学科学和癌症治疗。

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.