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 PI：Minko，Sergiy ORG：Clarkson University标题：远程控制药物输送材料：磁场引发的药物释放的生物催化机制技术：拟议的研究目标是为探索磁场引发的药物释放的生物催化机制的靶向特定药物释放系统的新的非侵入性方法开发基本和实用的方法。在研究团队先前在纳米粒子定向组装领域工作的基础上，本项目旨在设计共轭酶和模型药物的磁性纳米粒子载体。如果不施加磁场，粒子壳的具体设计将提供生理环境中的酶和药物的保护。最初由颗粒外壳筛选的药物和酶只有在磁场打开时才会被激活，并在磁场关闭后保持活性。当酶与药物紧密接触时，磁场脉冲将导致颗粒聚集体的形成，而药物由于酶作用下将药物结合到颗粒上的化学键的断裂而释放。拟议的研究计划涉及携带共轭酶和药物分子的磁性纳米颗粒的合成、功能化和表征。它包括研究这些颗粒的自组装以及在模拟细胞内外生物环境和活细胞的体外环境中磁场中组装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无污垢特性的亲水性聚合物(聚合物刷子)来设计颗粒外壳。酶和药物将被嵌入并结合到聚合物外壳中。壳层的组成和聚合物刷的分子特性将被优化，以平衡聚合物刷施加的空间斥力和磁场中诱导的吸引偶极-偶极相互作用。非技术：拟议的项目将设计一种新型的、坚固的、非侵入性的、选择性的和远程控制的药物输送系统平台，该平台可以进一步开发为抗癌药物、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进磁性药物靶向，这是最具吸引力的靶向给药的非侵入性方法之一，其中治疗药物被远程定向到患病组织。建议的方法应该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，同时允许利用磁性载体的对比特性来监测药物载体向病变组织及其周围的运输和分布。该研究计划将有助于教育和培养国家在先进科学技术方面的领导地位。这些影响将通过以下方式实现：利用研究小组的跨学科环境培训下一代专业人员，并讨论与项目有关的主题和由国际和平研究所教授的生物材料课程的发展情况。吸引高中生和本科生投身科学和职业生涯是计划中的外展活动的一个关键因素。将做出重大努力，增加攻读科学和工程高级学位的学生数量，特别是来自代表性较低群体的学生。该项目的外展部分将通过出版物、在会议上的介绍、发明、在地方和国家媒体上发表以及与潜在的工业伙伴、高中生和当地社区成员举行的研讨会和会议来实现。