Siglec-targeted nanoparticles for lung and cardiovascular disease

Siglec 靶向纳米粒子治疗肺和心血管疾病

• 批准号: 8184129
• 负责人: JAMES C PAULSON
• 金额: $ 49.75万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8184129
• 关键词: Affinity; Animal Model; Antibodies; Apolipoprotein E; Apoptosis; Arterial Fatty Streak; Asthma; Atherosclerosis; B-Cell Lymphomas; B-Lymphocytes; Blood Cells; CD22 antigen; CD22 gene; Cardiovascular Diseases; Cells; Chronic Obstructive Airway Disease; Collaborations; Diagnosis; Disease; Drug Formulations; Drug Kinetics; Endocytosis; Evaluation; Exhibits; Extrinsic asthma; Family; Gadolinium; Glycobiology; Human; Image; Immunologic Receptors; In Vitro; Inflammatory; Instruction; Interleukin-5; Label; Laboratories; Learning; Leukocytes; Ligands; Ligation; Liposomes; Lung; Lung Inflammation; Lung diseases; Magnetic Resonance Imaging; Mediating; Modeling; Motivation; Mus; Natural Immunity; Necrosis; Pathology; Play; Polymers; Polysaccharides; Population; Principal Investigator; Process; Property; Recruitment Activity; Role; Rupture; Sialic Acids; Signal Transduction; Site; Symptoms; Testing; Therapeutic Effect; Tissues; Transgenic Mice; Translating; Wild Type Mouse; adaptive immunity; base; cell killing; cell type; eosinophil; gadolinium oxide; human SIGLEC8 protein; in vivo; interest; killings; macrophage; monocyte; nanoparticle; neutrophil; novel; polyacrylamide; programs; receptor binding; research study; sialic acid binding Ig-like lectin; sialoadhesin; stem

This project is a component of the Lung Inflammatory Disease program of the Programs of Excellence in Glycosciences (LID-PEG). In this project we seel< to develop leukocyte targeted nanoparticles bearing glycan ligands of siglecs, and investigate their use in diagnosis and therapy of lung and cardiovascular diseases. The siglecs are a family of immune receptors that bind sialic acid containing glycans as ligands. Most siglecs are expressed on leukocytes and are well documented as regulators of cell signaling in innate and adaptive immunity. Because each siglec is expressed on one or a few cell types, they are well suited as targets for cell directed therapies for diseases caused by leukocytes. The applicant's laboratory has developed nanoparticle platforms decorated with siglec ligands that are capable of selectively targeting and delivering cargo to cells expressing the corresponding siglec. In the proposed project we will use these nanoparticles to target leukocytes that play critical roles in the initiation and progression of lung and cardiovascular disease. Nanoparticles decorated with ligands to Siglec-8 (murine Siglec-F) will be used to target eosinophils, Siglec-9 (murine Siglec-E) to target neutrophils, and sialoadhesin (Sn; Siglec-1) to target monocytes/macrophages. Nanoparticles targeting each leukocyte cell type will be tested for their activity in murine models of allergic asthma and chronic obstructive pulmonary disease (COPD), and sialoadhesin (macrophage) targeted nanoparticles will be tested for diagnosis and amelioration of atherosclerotic plaque in a murine model of atherosclerosis. The results will help establish the roles of the corresponding cell types in disease processes, and document the potential utility of siglec- targeted nanoparticles in the diagnosis and treatment of lung and cardiovascular disease. RELEVANCE (See instructions): This project seeks to develop novel cell targeted nanoparticles that can deliver agents to white blood cells for diagnosis and treatment of lung and cardiovascular diseases.

该项目是肺部炎症疾病计划的组成部分，该计划的卓越计划 糖基镜（LID-PEG）。在这个项目中，我们开始<开发白细胞靶向纳米颗粒的轴承 siglecs的聚糖配体，并研究它们在肺和心血管诊断和治疗中的使用 疾病。 Siglecs是一个免疫受体家族，它们结合含有聚糖作为配体的唾液酸。 大多数Siglecs在白细胞上表达 先天和适应性免疫。因为每个siglec在一种或几种单元类型上都表达，所以它们很好 适用于白细胞引起的细胞定向疗法的靶标。申请人的实验室 已经开发了纳米颗粒平台，该平台装饰有siglec配体，能够有选择性 将货物靶向和传递到表达相应SIGLEC的细胞。在拟议的项目中我们 将使用这些纳米颗粒来靶向白细胞，该白细胞在开始和进展中起关键作用 肺和心血管疾病。纳米颗粒装饰有配体的siglec-8（鼠siglec-f）将 用于靶向嗜酸性粒细胞，Siglec-9（鼠Siglec-e）靶向嗜中性粒细胞和核粘附素（SN; SIGLEC-1）靶向单核细胞/巨噬细胞。针对每种白细胞细胞类型的纳米颗粒将是 在过敏性哮喘和慢性阻塞性肺疾病的鼠模型中测试了它们的活性 （COPD）和核粘附素（巨噬细胞）靶向纳米颗粒将进行诊断和 在动脉粥样硬化的鼠模型中，动脉粥样硬化斑块的改善。结果将有助于建立 相应细胞类型在疾病过程中的作用，并记录了Siglec-的潜在效用 靶向纳米颗粒在肺和心血管疾病的诊断和治疗中。 相关性（请参阅说明）： 该项目旨在开发具有新型细胞靶向纳米颗粒，这些纳米颗粒可以将剂传递给白细胞 肺和心血管疾病的诊断和治疗。