Engineering Multifunctional Nanoparticles

描述(申请人提供)：最近，出现了一种新的纳米材料的爆炸性增长，有可能影响医学和人类健康。将这些发现转化为恶性肿瘤的早期诊断和有效治疗是NCI设定的关键临床目标。因此，这项BRP专注于多功能纳米颗粒的工程设计，这种纳米颗粒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。这个多学科团队的成员在生物医学工程(麻省理工学院Sangeeta Bhatia博士)、化学和材料科学(Michael Sailor博士，加州大学圣地亚哥分校)和肿瘤生物学(Erkki Ruola hti博士，伯纳姆研究所)方面拥有互补的专业知识，并在合作发明、学生监督、资助和出版方面有着良好的记录。在当前靶向技术效率低下的激励下，我们试图设计纳米颗粒来模拟血小板在血管损伤特定部位的靶向聚集。我们进一步寻求利用纳米材料集合的紧急特性，以提高肿瘤部位堆积的成像和药物输送能力。因此，多功能纳米颗粒将基于葡聚糖包被的氧化铁纳米颗粒，其工程目的是：(1)通过噬菌体展示衍生多肽来靶向肿瘤；(2)通过蛋白酶激活和血浆蛋白质辅助捕获在肿瘤中进行自我组装；(3)通过磁共振成像检测T2弛豫度的变化；以及(4)通过使用电磁场的远程激活来输送药物。这项工作将分为三个领域，代表参与实验室的专业知识。赛勒博士的团队将开发并表征这种载药的超顺磁性材料。罗斯拉蒂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展示鉴定新肽的方法。巴蒂亚博士的专长在于探测细胞界面的微米和纳米技术工具。她的角色将是设计出可以进行触发自组装、远程驱动和活体成像的纳米颗粒。这些技术和研究人员的结合有望导致新一代纳米设备的开发，这种设备将显著促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.