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

生态旅游- 0829128 k。这项合作研究的总体目标是对生物相容性核（金纳米棒）-壳（层状双氢氧化物或LDH）纳米颗粒的工程和机械理解，以选择性递送siRNA，并加强热疗治疗。所提出的纳米颗粒中的特定片段专门用于(1)高温消融和(2)携带抑制热休克蛋白对高温反应的siRNA。因此，拟议的研究采用自下而上的纳米尺度工程来直接影响生物医学问题。LDH结构是一类无机陶瓷材料，其通式为M2+1(1-x)M3+(OH)2.(An-)x/n。mH2O，其中M2+为二价阳离子，M3+为三价阳离子，An-为n价层间阴离子。独特的LDH结构易于通过离子交换插入阴离子分子（如siRNA）；改变金属离子的比例导致这些纳米颗粒中siRNA的可调负载。纳米级LDH壳可以使用生理上必需的金属（如铁和锌）生成，从而避免了与毒性有关的问题。此外，乳酸脱氢酶外壳在内体/溶酶体晚期（酸性）pH下的解体导致环境响应平台。主要目标是：(1)合成和表征具有窄尺寸分布的金纳米棒- ldh纳米颗粒；(2)生成装载siRNA的核-壳纳米颗粒；(3)体外评估使用核-壳纳米结构的siRNA传递和联合处理。在单个纳米颗粒上同时递送siRNA和热消融是所提出的平台的独特属性，并且可以显着提高肿瘤细胞消融的治疗效果。拟议研究的成功完成将产生一个可扩展到各种生物医学应用的平台。这项研究是纳米技术和生物医学科学的结合，将纳米粒子合成、热疗、表面化学、生物分子吸附和细胞生物学的原理协同结合，有望在不久的将来对生物医学科学产生直接影响。研究生将接受纳米技术在生物医学科学中的应用方面的培训，从而在工程和生物医学科学方面进行全面的跨学科培训。教育的重点还在于招收代表性不足的人口和妇女参加工程研究生学习，目前我们各自研究小组的研究生就是一个例子。此外，PI最近还开始与美国国家科学基金会资助的亚利桑那州立大学GK-12项目“脚踏实地科学”（DES）合作（http://gk12.asu.edu）。PI和Co-PI以及研究生将与DES项目的主任、工作人员和研究生合作，通过讲座和基于网络的教育工具将纳米技术的生物医学益处引入K-12教室。拟议的研究也将对本科教育产生重大影响，特别强调纳米技术的生物医学效益。六名本科生，其中四名来自巴雷特荣誉学院，在PI的实验室，两名本科生在亚利桑那州立大学的联合PI实验室，这体现了我们鼓励有才华的学生追求研究机会和工程研究生学习的承诺。PI的所有本科生？美国亚利桑那州立大学Ira a . Fulton工程学院的富尔顿本科生研究计划（FURI）奖是一个独特的项目，鼓励本科生在工程方面的研究。

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.