Biocompatible Metal (Core)-Layered Double Hydroxide (Shell) Nanoparticles for siRNA Delivery

用于 siRNA 递送的生物相容性金属（核）层状双氢氧化物（壳）纳米粒子

• 批准号: 0829128
• 负责人: Kaushal Rege
• 金额: $ 24万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0829128&HistoricalAwards=false
• 关键词: Biocompatible; Metal; Core; Layered; Double

CBET-0829128K. Rege, Arizona State UniversityThe overall objective of this collaborative research is the engineering and mechanistic understanding of biocompatible core (gold nanorod)-shell (layered-double hydroxide or LDH) based nanoparticles for selective delivery of siRNA with an eye towards enhancing hyperthermia treatments. Specific segments in the proposed nanoparticle are dedicated to (1) hyperthermic ablation and (2) carrying siRNA for inhibiting heat shock protein response to hyperthermia. The proposed research, therefore, employs bottom-up nanoscale engineering for direct impact in biomedical problems.LDH structures are a class of inorganic ceramic materials with the general formula M2+1(1-x)M3+(OH)2.(An-)x/n.mH2O, where M2+ is a divalent cation, M3+ is a trivalent cation, and An- is the interlayer anion of valence n. The unique LDH structure readily allows the intercalation of anionic molecules (e.g. siRNA) via ion exchange; varying the ratios of metal ions results in the tunable loading of siRNA in these nanoparticles. Nanoscale LDH shells may be generated using physiologically necessary metals (e.g. iron and zinc), thus obviating toxicity-related concerns. Furthermore, the disintegration of the LDH shell at late endosomal / lysozomal (acidic) pH results in an environmentally-responsive platform. The primary objectives are: (1) synthesis and characterization of gold nanorod-LDH nanoparticles with narrow size distribution profiles, (2) generation of siRNA-loaded core-shell nanoparticles, and (3) in-vitro evaluation of siRNA delivery and combination treatment using core-shell nanostructures. Simultaneous siRNA delivery and hyperthermic ablation on a single nanoparticle are unique attributes of the proposed platform, and can significantly enhance therapeutic efficacies for the ablation of cancer cells. Successful completion of the proposed research will result in a platform that can be extended to diverse biomedical applications.The proposed research, at the interface of nanotechnology and biomedical sciences, synergistically combines principles from nanoparticle synthesis, hyperthermia, surface chemistry, biomolecular adsorption, and cell biology, and is intended to have a direct impact on biomedical sciences in the near future. Graduate students will be trained in the application of nanotechnology in the biomedical sciences resulting in well rounded, interdisciplinary training in engineering and biomedical sciences. The educational thrust is also on the recruitment of underrepresented populations and women in graduate studies in engineering as exemplified by the graduate students currently in our respective research groups. In addition, the PI has recently initiated collaboration with Down-to-Earth Science (DES), an NSF-funded GK-12 project at Arizona State University (http://gk12.asu.edu). The PI and Co-PI, and the graduate students will partner with the director, staff, and graduate students of the DES program in bringing the biomedical benefits of nanotechnology into K-12 classrooms through lectures and web-based education tools. The proposed research will also have a significant impact on undergraduate education with a particular emphasis on the biomedical benefits of nanotechnology. Six undergraduate students, including four from the Barrett Honors College, in the PI's laboratory and two undergraduate students in the co-PI's laboratory at ASU exemplify our commitment to encouraging talented students to pursue research opportunities and graduate studies in engineering. All undergraduate students in the PI?s laboratory are recipients of the Fulton Undergraduate Research Initiative (FURI) award from the Ira A. Fulton School of Engineering at ASU which is a unique program that encourages undergraduate research in engineering.

CBET-0829128K。亚利桑那州立大学雷格，这项合作研究的总体目标是对生物相容性核心（Gold nanorod）壳（分层双氢氧化物或LDH）纳米颗粒的工程和机械理解，可选择性地递送siRNA，以朝着增强高温治疗的目光注视。拟议的纳米颗粒中的特定段专用于（1）（1）过度疗法和（2）携带siRNA来抑制热休克蛋白对高温的反应。因此，提出的研究采用自下而上的纳米级工程来直接影响生物医学问题。LDH结构是一类带有一般式M2+ 1（1-X）M3+（OH）的无机陶瓷材料。独特的LDH结构易于通过离子交换来插入阴离子分子（例如siRNA）；金属离子的比例改变导致这些纳米颗粒中siRNA的可调载荷。可以使用生理上必要的金属（例如铁和锌）生成纳米级LDH壳，从而避免了与毒性相关的问题。此外，在晚期内体 /溶菌酶（酸性）pH下LDH壳的瓦解导致环境响应的平台。主要目标是：（1）具有较窄尺寸分布曲线的金纳米棒LDH纳米颗粒的合成和表征，（2）siRNA负载的核心壳纳米颗粒的产生，以及（3）使用Core-Shell纳米结构对siRNA递送和组合处理的siRNA递送和组合处理。同时在单个纳米颗粒上同时siRNA递送和过度热平均是该拟议平台的独特属性，并且可以显着提高癌细胞消融的治疗效率。拟议的研究的成功完成将导致一个可以扩展到多种生物医学应用的平台。拟议的研究，在纳米技术和生物医学科学的界面上，协同结合了纳米粒子同步，超细热，表面化学，生物分析，生物分析和细胞生物学和生物生物学的原理，并在生物学上均具有良好的影响。研究生将接受纳米技术在生物医学科学中的应用，从而在工程和生物医学科学领域进行圆形，跨学科的培训。教育推力还与当前各自研究小组中的研究生典范的招募人群招募人数不足的人群和妇女在工程学研究生研究中。此外，PI最近与Arizona州立大学（http://gk12.asu.edu）的NSF资助的GK-12项目（DES）合作。 PI和Co-Pi以及研究生将与DES计划的导演，教职员工和研究生合作，通过讲座和基于Web的教育工具将纳米技术的生物医学益处带入K-12教室。拟议的研究还将对本科教育产生重大影响，并特别着重于纳米技术的生物医学益处。 ASU的Co-Pi实验室中的六名本科生，其中包括Barrett Honors学院的四名学生和两名本科生，这表明了我们鼓励才华横溢的学生寻求研究机会和工程研究生研究的承诺。 PI的实验室中的所有本科生都是ASU的IRA A. Fulton工程学院的Fulton本科研究计划（FURI）奖的获得者，这是一项独特的计划，鼓励工程研究本科研究。