Remote Controlled Drug Delivery Material: Bio Catalytic Mechanisms of Drug Release Triggered by Magnetic Field

遥控给药材料：磁场触发药物释放的生物催化机制

• 批准号: 1426193
• 负责人: Sergiy Minko
• 金额: $ 36万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-05 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1426193&HistoricalAwards=false
• 关键词: Remote; Controlled; Drug; Delivery; Material

ID: MPS/DMR/BMAT(7623) 1309469 PI: Minko, Sergiy ORG: Clarkson UniversityTitle: Remote Controlled Drug Delivery Material: Biocatalytic Mechanisms of Drug Release Triggered by a Magnetic FieldTechnical: The goal of the proposed research is to develop fundamental and practical approaches for novel non-invasive methods of target-specific drug delivery systems that explore biocatalytic mechanisms of drug release triggered by a magnetic field. Building on the previous work of the research team in the field of directed assembly of nanoparticles, this project aims at the design of magnetic nanoparticle carriers of conjugated enzymes and model drugs. The specific design of the particle shell will provide conservation of the enzymes and drugs in the physiological environment if no magnetic field is applied. The drug and the enzyme initially screened by the particle shell become activated only if the magnetic field is turned on, and remain active after the magnetic field is turned off. A magnetic field pulse will result in the formation of particle aggregates when the enzyme and the drug are in a close contact and the drug is released due to enzymatic cleavage of the chemical bond that binds the drug to the particle. The proposed research plan involves the synthesis, functionalization, and characterization of the magnetic nanoparticles that carry conjugated enzymes and drug molecules. It includes study of the self-assembly of these particles and the related biocatalytic activity of the assemblies in a magnetic field in an in vitro environment that mimics extracellular and intracellular biological environments and in living cells. To accomplish this goal, the research team will design the particle shell using hydrophilic polymers (polymer brushes) with non-fouling properties. The enzymes and drugs will be embedded into and bound to the polymer shell. The composition of the shell and molecular characteristics of the polymer brush will be optimized to balance the steric repulsive forces exerted by the polymer brushes and attractive dipole-dipole interactions induced in the magnetic field. Non-Technical: The proposed project will design a novel, robust, non-invasive, selective, and remotely controlled drug delivery system platform that can be further developed toward delivery systems for anticancer drugs, anti-inflammatories, and contrast agents as well as for tissue engineering and biosensor applications. This work will further improve magnetic drug targeting, one of the most attractive non-invasive methods for target-specific drug delivery, wherein therapeutic medicines are directed remotely to a diseased tissue. The proposed approach should reduce the side effects associated with the non-specific uptake of cytotoxic drugs by healthy tissue and simultaneously allow monitoring of the transport and distribution of drug carriers to and around the diseased tissue using the contrast properties of the magnetic carrier. The research program will contribute to both the education and growth of national leadership in advanced science and technology. These impacts will be realized by training the next generation of professionals using the interdisciplinary environment of the research team and discussing project-related topics and developments in the Biomaterials course taught by the PI. Attracting high school and undergraduate students to scientific and professional careers is a key element of the planned outreach. Significant efforts will be directed toward increasing the number of students, especially from underrepresented groups, who pursue advanced degrees in science and engineering. The outreach components of the project will be realized through publications, presentations at conferences, inventions, publication in local and national media, and seminars and meetings with potential industrial partners, high school students, and local community members.

ID：MPS/DMR/BMAT（7623）1309469 主要研究者：Minko，Sergiy ORG：克拉克森大学远程控制药物递送材料：由磁场触发的药物释放的生物催化机制技术：拟议研究的目标是为靶向药物递送系统的新型非侵入性方法开发基本和实用的方法，该方法探索由磁场触发的药物释放的生物催化机制。 该项目在研究团队先前在纳米粒子定向组装领域的工作基础上，旨在设计结合酶和模型药物的磁性纳米粒子载体。 如果不施加磁场，颗粒壳的特定设计将提供生理环境中酶和药物的保存。 最初被粒子壳屏蔽的药物和酶只有在磁场打开时才被激活，并且在磁场关闭后保持活性。 当酶和药物紧密接触时，磁场脉冲将导致颗粒聚集体的形成，并且由于将药物结合到颗粒的化学键的酶促裂解而释放药物。 拟议的研究计划涉及合成，功能化和表征的磁性纳米粒子，携带共轭酶和药物分子。 它包括研究这些粒子的自组装和组装体在模拟细胞外和细胞内生物环境和活细胞的体外环境中在磁场中的相关生物催化活性。 为了实现这一目标，研究小组将使用具有非污垢特性的亲水聚合物（聚合物刷）设计颗粒外壳。 酶和药物将嵌入并结合到聚合物壳中。 壳的组成和聚合物刷的分子特性将被优化以平衡由聚合物刷施加的空间排斥力和在磁场中诱导的吸引性偶极-偶极相互作用。非技术：拟议的项目将设计一种新型的，稳健的，非侵入性的，选择性的和远程控制的药物输送系统平台，可以进一步开发抗癌药物，抗炎药和造影剂以及组织工程和生物传感器应用的输送系统。 这项工作将进一步改善磁性药物靶向，这是靶向药物递送的最有吸引力的非侵入性方法之一，其中治疗药物被远程引导到患病组织。 所提出的方法应减少与健康组织对细胞毒性药物的非特异性摄取相关的副作用，同时允许使用磁性载体的对比特性监测药物载体向患病组织及其周围的运输和分布。 该研究计划将有助于教育和先进科学技术的国家领导力的增长。 这些影响将通过使用研究团队的跨学科环境培训下一代专业人员并讨论PI教授的生物材料课程中与项目相关的主题和发展来实现。 吸引高中生和本科生从事科学和专业职业是计划中的外联活动的一个关键要素。 将大力增加攻读科学和工程高级学位的学生人数，特别是来自代表性不足群体的学生人数。 该项目的外联部分将通过出版物、在会议上的介绍、发明、在地方和国家媒体上的出版物以及与潜在的工业伙伴、高中生和地方社区成员举行的研讨会和会议来实现。