NIR Light-Activated Nanoparticles for Drug and Gene Delivery

用于药物和基因递送的近红外光激活纳米颗粒

基本信息

批准号：
8027621
负责人：
Joseph Anthony Zasadzinski
金额：
$ 9.99万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-15 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8027621
关键词：
Address Antibodies Basic Science Benign Biocompatible Biological Biological Process Bypass Caenorhabditis elegans Caliber Cancer Biology Cell Culture Techniques Cell Line Cells Chemicals Chemistry Combination Drug Therapy Complex Cultured Cells Cytosol DNA Development Drug Controls Drug Delivery Systems Endosomes Epithelial Cells Exposure to Gene Delivery Gene Silencing Genes Genetic Materials Goals Gold Heating Hela Cells Image Label Life Ligands Light Link Lipids Lipofectamine Liposomes Malignant neoplasm of prostate Mammalian Cell Masks Methods MicroRNAs Microbubbles Molecular Mus Oligonucleotides Optics Organism Pattern Pharmaceutical Preparations Physiologic pulse Polymers Property Proteins RNA Interference Resolution Route Rupture Signal Transduction Pathway Silver Site Small Interfering RNA Source Structure Sulfhydryl Compounds Surface Suspension substance Suspensions Techniques Therapeutic Thick Time Tissues Toxic effect Transfection Water Work absorption base cell injury cell type chemical property chemotherapy controlled release design dithiol human embryonic stem cell human stem cells in vivo irradiation lithography millisecond nanomaterials nanoparticle nanorod nanoscale nanoshell novel physical property receptor research study small molecule stem cell differentiation targeted delivery vapor

项目摘要

DESCRIPTION (provided by applicant): Our goal is to develop robust siRNA and micro-RNA methods to regulate genes for basic research, permitting both temporal and spatial control of transfection with high efficiency in both cell culture and C. elegans by using the unique chemical and physical properties of hollow gold nanoshells (HGN). HGNs are 30 - 40 nm diameter, 3-5 nm thick, gold shells designed to strongly absorb physiologically friendly NIR light and convert this light energy into local heating. HGN can be easily conjugated to small molecules, targeting ligands, polymers, siRNA and DNA by simple thiol chemistry, or incorporated into or tethered to liposomes. Water, proteins, lipids, etc. do not absorb NIR light, so cells in culture are essentially transparent, which eliminates damage during exposure. Femtosecond NIR light pulses trigger release of thiol-conjugated siRNA or other molecules from the HGN by breaking thiol bonds without damaging the siRNA. Even more important to the development of efficient oligonucleotide and small molecule delivery, the well-known bottleneck of endosomal escape can be bypassed by converting the physiologically friendly NIR light energy absorbed by the HGN to heat, creating unstable microbubbles that mechanically rupture endosomes and release siRNA to the cytosol within seconds. This allows much lower concentrations of HGN-siRNA conjugates to be used, greatly increases transfection efficiency, and provides spatially and temporally controlled transfection that can be used to pattern cultured cells and address specific structures within C. elegans. HGN transfection is as efficient as Lipofectamine, but is non-toxic, and can be used in living organisms. In this proposal, we will use the HGN-siRNA platform to develop masking and unmasking techniques for activating or inactivating biological processes with remote control to devise simple and scalable methods of lithographic patterning of cultured cells in real time. We will investigate controlled release of small molecules from liposomes incorporating HGN using NIR light triggering to control release, thereby enabling basic cell biological studies, including human stem cell differentiation, cancer biology, and signal transduction pathways and routes to applications in chemotherapy and drug delivery. We will develop methods to multiplex the release from a single HGN using a combination of thiol and dithiol anchors that desorbs at different energies to release of multiple chemical species. New silver nanoshells and gold and silver nanorods will be synthesized to probe other regions of the NIR spectrum and provide simultaneous delivery and imaging opportunities. These new constructs could be addressed independently by using different wavelength NIR irradiation. This project takes full advantage of the unique HGN interactions with physiologically friendly NIR light to initiate and control biological processes with precise spatial control at millisecond rates in living cells and organisms.

描述（由申请人提供）：我们的目标是开发强大的siRNA和微RNA方法，以调节基因进行基础研究，从而通过使用空心金纳米壳（HGN）的独特化学和物理性能在细胞培养和秀丽隐杆线虫中对转染的时间和空间控制。 HGNS的直径为30-40 nm，厚3-5 nm，旨在强烈吸收生理上友好的NIR光，并将这种光能转化为局部加热。 HGN可以很容易地与小分子结合，通过简单硫醇化学靶向配体，聚合物，siRNA和DNA，或掺入或绑扎到脂质体中。水，蛋白质，脂质等不吸收NIR光，因此培养中的细胞本质上是透明的，从而消除了暴露期间的损害。飞秒的NIR光脉冲触发了硫醇偶联的siRNA或其他分子从HGN释放，而不会破坏硫醇键而不会损坏siRNA。对于有效的寡核苷酸和小分子递送的开发，更重要的是，可以通过将HGN吸收的生理友好的NIR光能转换为热量，从而绕开众所周知的内体逃生瓶颈，从而在机械上破裂的内体并释放出sirna，并在秒内释放sirna。这允许使用较低浓度的HGN-SIRNA结合物，大大提高转染效率，并提供空间和时间控制的转染，可用于对秀丽隐杆线虫内的特定结构进行模拟。 HGN转染与Lipofectamine一样有效，但无毒，可用于活生物体。在此提案中，我们将使用HGN-SIRNA平台来开发掩盖和揭示具有遥控器的生物学过程的激活或灭活生物学过程，以实时设计简单且可扩展的培养细胞的光刻图案方法。我们将研究使用NIR光触发HGN从脂质体中释放的小分子来控制释放，从而实现基本细胞生物学研究，包括人类干细胞分化，癌症生物学以及信号转导途径以及在化学疗法和药物递送中应用的途径。我们将使用硫醇和二硫醇锚固剂的组合来开发从单个HGN释放的方法，这些硫醇和二硫醇锚以不同能量的释放多种化学物种的释放。新的银纳米壳以及黄金和银色纳米棒将合成以探测NIR光谱的其他地区，并同时提供交付和成像机会。这些新构建体可以通过使用不同的波长NIR辐射独立解决。该项目充分利用了与生理友好型NIR光的独特相互作用，以启动和控制生物学过程，并以精确的空间控制在活细胞和生物体中以毫秒的速率进行。