Nanoparticle mediated in vivo cell-type specific drug delivery for pain relief

纳米颗粒介导体内细胞类型特异性药物递送以缓解疼痛

• 批准号: 8364809
• 负责人: ZHIGANG David LUO
• 金额: $ 22.18万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364809
• 关键词: Adverse effects; Analgesics; Animal Model; Antibodies; Binding; Cells; Clinical; Complex; Confocal Microscopy; Coupling; Data; Detection; Development; Dorsal; Dose; Drug Delivery Systems; Endocytosis; Fc Receptor; Gene Silencing; Intrathecal Injections; Label; Lead; Ligands; Mediating; Mediator of activation protein; Medical; Nanotechnology; Neurons; Pain; Pain management; Peptides; Pharmaceutical Preparations; Process; RNA Interference; Rattus; Receptor Gene; Role; Signal Transduction; Specificity; Spinal; Spinal Cord; Spinal Ganglia; Staining method; Stains; Stimulus; Substance P; Substance P Receptor; Syndrome; Techniques; Technology; Testing; Therapeutic Agents; Time; United States National Institutes of Health; cell type; chronic pain; improved; in vivo; insight; knock-down; nanoparticle; preference; receptor; receptor expression; receptor internalization; research study; tool; uptake

DESCRIPTION (provided by applicant): Existing data support a critical role of neurokinin 1 receptor (NK1 receptor) expressing neurons in the dorsal spinal cord in mediating pain processing. Taking the advantage of newly developed nanoparticles, we propose to study in this exploratory proposal whether conjugation of nanoparticles with Substance P, a pain- inducing peptide and specific ligand to NK1 receptors, can achieve cell-type specific delivery of small interference RNA (siRNA) into NK1 receptor expressing cells upon ligand-induced endocytosis, and if so, whether this approach can lead to effective gene silencing and pain relief in animal models. We will first study the optimal dose and time point for nanoparticle distributio in vivo. Second, we will examine nanoparticle distribution in different cell types. Third, we wil examine if this approach can be used for in vivo NK1 receptor gene silencing and blocking pain processing in animal models. Promising data derived from this project will be used for the application of a larger scale NIH R01 project related to application of siRNA/nanoparticles in targeted gene silencing and pain relief. PUBLIC HEALTH RELEVANCE: Chronic pain is a common clinical syndrome lacking specific, effective and safe therapeutic agents. Taking the advantage of newly developed nanoparticles, we plan to study whether conjugation of a ligand specific to pain-mediating receptors to nanoparticles can improve cell-type specific delivery of small interference RNA (siRNA) for effective gene silencing and pain relief in vivo. Completion of this study will allow us to gain insights into the potential use of nanoparticles as a carrier for cell-type specific drug delivery n vivo.

描述（由申请方提供）：现有数据支持脊髓背侧神经激肽1受体（NK 1受体）表达神经元在介导疼痛处理中的关键作用。 利用新开发的纳米颗粒的优势，我们提出在该探索性提议中研究纳米颗粒与物质P（疼痛诱导肽和NK 1受体的特异性配体）的缀合是否可以在配体诱导的内吞作用后实现小干扰RNA（siRNA）到NK 1受体表达细胞中的细胞类型特异性递送，并且如果是这样，这种方法是否可以在动物模型中导致有效的基因沉默和疼痛缓解。 我们将首先研究纳米颗粒在体内分布的最佳剂量和时间点。 其次，我们将研究纳米颗粒在不同细胞类型中的分布。 第三，我们将检查这种方法是否可以用于在动物模型中的体内NK 1受体基因沉默和阻断疼痛处理。 来自该项目的有希望的数据将用于与siRNA/纳米颗粒在靶向基因沉默和疼痛缓解中的应用相关的更大规模NIH R 01项目的应用。 公共卫生相关性：慢性疼痛是一种常见的临床综合征，缺乏特异性、有效和安全的治疗药物。 利用新开发的纳米颗粒，我们计划研究是否共轭的配体特异性疼痛介导受体的纳米颗粒可以提高细胞类型特异性传递的小干扰RNA（siRNA）有效的基因沉默和疼痛缓解在体内。 这项研究的完成将使我们能够深入了解纳米颗粒作为细胞类型特异性药物递送载体的潜在用途。