Engineering and characterizing nanoparticles for cancer targeting

用于癌症靶向的纳米粒子的工程和表征

• 批准号: 1159967
• 负责人: Efrosini Kokkoli
• 金额: $ 14.5万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1159967&HistoricalAwards=false
• 关键词: Engineering; characterizing; nanoparticles; cancer; targeting

1159967/ Kokkoli This NSF award by the Interfacial Processes and Thermodynamics and the Biotechnology, Biochemical and Biomass Engineering programs supports the development of novel aptamer functionalizes stealth liposomes that bind to a new cell surface molecule (fractalkine) on cells associated with cancer and inflamation. Aptamers are short single-stranded oligonucleotides. They are chemically produced, have the capability of binding with high affinity and specificity a variety of different targets, and have been shown to be useful as therapeutic agents and diagnostic tools. Their affinities are often comparable to those observed for monoclonal antibodies, and are significantly higher compared to those of peptides. As aptamer-amphiphiles, aptamers attached to a hydrophobic tail, they can assemble with other lipids into liposomes that can be used as targeted nanoparticles to treat different diseases, including cancer. Researchers will engineer and characterize in vitro fractalkine targeted stealth liposomes and evaluate their binding affinity and specificity for fractalkine expressing colon cancer cells, as well as internalization and trafficking by these cells. These experiments will identify the optimal aptamer concentration that will be used for the design of the targeted delivery system. The PI will then characterize the aptamer functionalized nanoparticles in vivo and evaluate their ability to reach the tumor site selectively in a murine model of colorectal cancer while avoiding health areas, as well as its efficacy and toxicity. For this task the nanoparticles will be loaded with doxorubicin. The innovative aspect of this proposal is the proposed use of the novel molecule, fractalkine, as a target for the delivery of nanoparticles that encapsulate a therapeutic payload. The proposed work will be of fundamental but also of practical significance as the engineered aptamer-functionalized stealth liposomes that will result from this study can be used as targeting nanoparticles in different applications and encapsulate different loads of interest.The PI integrates her research with her educational plan. One educational activity focuses on targeting underrepresented minority students at the Saint Paul College, A Community & Technical College (with a large representation of a wide range of minority populations) with the focus of exposing them to the research performed in the PI's lab, and motivating them to transition into four-year colleges and universities. The PI is currently collaborating, and will continue to do so in the future, with MRSEC. Through MRSEC the PI will be hosting during the summer high school teachers, and minority undergraduates from a nationwide pool of applicants, through a well established network of high schools, and minority undergraduates from a number of Minority Serving Institutions. To further attract underrepresented minority undergraduates in the her laboratory, the PI will be attending and presenting at the North Star STEM Alliance symposium. Furthermore, the PI has participated, and will continue to participate, in outreach activities organized by different organizations and societies with the goal of attracting and mentoring women in sciences and engineering (a long term goal for the PI). As part of this goal the PI is proposing to organize a seminar series in the Department of Chemical Engineering and Materials Science at theUniversity of Minnesota, entitled "Women Engineers in Academia and Industry" with monthly seminars given by women that will serve as positive role models for the female students and postdocs.

1159967/ Kokkoli该NSF奖项由界面过程和热力学以及生物技术，生物化学和生物质工程计划提供，支持开发新型适体功能化隐形脂质体，该脂质体与癌症和炎症相关细胞上的新细胞表面分子（fractalkine）结合。适体是短的单链寡核苷酸。它们是化学产生的，具有以高亲和力和特异性结合多种不同靶标的能力，并且已显示可用作治疗剂和诊断工具。它们的亲和力通常与单克隆抗体所观察到的亲和力相当，并且与肽的亲和力相比显著更高。作为适配体-两亲物，适配体连接到疏水尾部，它们可以与其他脂质组装成脂质体，脂质体可以用作靶向纳米颗粒来治疗不同的疾病，包括癌症。研究人员将设计和表征体外fractalkine靶向隐形脂质体，并评估它们对表达fractalkine的结肠癌细胞的结合亲和力和特异性，以及这些细胞的内化和运输。这些实验将确定用于靶向递送系统设计的最佳适体浓度。 然后PI将在体内表征适体功能化纳米颗粒，并评估其在结肠直肠癌小鼠模型中选择性到达肿瘤部位同时避开健康区域的能力，以及其疗效和毒性。对于该任务，纳米颗粒将装载有阿霉素。该提案的创新方面是提出使用新型分子fractalkine作为递送封装治疗有效载荷的纳米颗粒的靶点。拟议的工作将是基本的，但也具有实际意义的工程适配体功能化的隐形脂质体，将从这项研究中产生的，可以用作靶向纳米粒子在不同的应用和封装不同的负载感兴趣的PI整合她的研究与她的教育计划。 一项教育活动的重点是针对圣保罗学院的少数民族学生，这是一所社区技术学院（有大量少数民族人口的代表），重点是让他们接触PI实验室进行的研究，并激励他们过渡到四年制学院和大学。PI目前正在与MRSEC合作，未来将继续这样做。通过MRSEC，PI将在夏季接待高中教师，并通过完善的高中网络从全国范围内的申请人中挑选少数民族本科生，以及来自一些少数民族服务机构的少数民族本科生。为了进一步吸引在她的实验室代表性不足的少数民族本科生，PI将出席并出席北星星干联盟研讨会。此外，PI已经并将继续参加不同组织和社团组织的外联活动，目的是吸引和指导科学和工程领域的妇女（PI的长期目标）。作为这一目标的一部分，PI建议在明尼苏达大学化学工程和材料科学系举办一系列研讨会，题为“学术界和工业界的女工程师”，每月由妇女举办研讨会，为女学生和博士后树立积极的榜样。