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: 1309469
• 负责人: Sergiy Minko
• 金额: $ 36万
• 依托单位: Clarkson University
• 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: 2013-09-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309469&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 Universitytitle：遥控药物交付材料：磁性现场技术触发的药物释放的生物催化机制：磁场技术的目标：提出的研究的目标是开发基本和实践方法的方法。由磁场触发的药物释放的生物催化机制。 该项目的基础是在定向纳米颗粒的定向组装领域的先前工作，旨在设计共轭酶和模型药物的磁性纳米颗粒载体。 如果未应用磁场，则颗粒壳的特定设计将在生理环境中提供酶和药物的保护。 最初仅在磁场打开磁场并关闭磁场后保持活跃的药物和最初由颗粒壳筛选的酶被激活。 当酶和药物处于密切接触时，由于化学键的酶促裂解，磁场脉冲将导致颗粒聚集体的形成，并释放该药物，该化学键将药物与颗粒结合在一起。 提出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磁场中组合的相关生物催化活性，这些体外环境模仿细胞外和细胞内生物学环境以及活细胞中。 为了实现这一目标，研究团队将使用具有非污染特性的亲水性聚合物（聚合物刷）来设计颗粒壳。 酶和药物将嵌入并结合到聚合物壳中。 聚合物刷的壳和分子特性的组成将被优化，以平衡由聚合物刷施加的空间排斥力以及在磁场中诱导的有吸引力的偶极偶极相互作用。非技术：拟议的项目将设计一种新颖，健壮，无创，选择性和远程控制的药物输送系统平台，可以进一步开发用于用于抗癌药物，抗炎药以及对比剂以及组织工程和生物传感器应用的抗癌药物的输送系统。 这项工作将进一步改善磁性药物的靶向，这是针对靶向药物递送的最有吸引力的非侵入性方法之一，其中治疗药物远程针对患病组织。 提出的方法应减少与健康组织对细胞毒性药物非特异性摄取相关的副作用，并同时使用磁载体的对比特性监测药物载体向患病组织和周围的传输。 该研究计划将有助于高级科学技术领导力的教育和发展。 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来实现这些影响，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。 吸引高中和本科生从事科学和职业职业是计划推广的关键要素。 重大努力将致力于增加学生的数量，尤其是来自代表性不足的群体，他们攻读科学和工程学的高级学位。 该项目的外展组成部分将通过出版物，会议，发明，本地和国家媒体的出版物以及与潜在的工业伙伴，高中生和当地社区成员的研讨会以及会议来实现。