Developing immunotherapeutic nanoparticles for spinal cord injury

开发用于脊髓损伤的免疫治疗纳米颗粒

• 批准号: 10569675
• 负责人: Jonghyuck Park
• 金额: $ 26.17万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569675
• 关键词: Acute; Anatomy; Binding; Cells; Centers of Research Excellence; Clinical Trials; Diagnosis; Environment; Equilibrium; FDA approved; Female; Formulation; Glycolic-Lactic Acid Polyester; Goals; Hospitals; Immune; Immunotherapeutic agent; Impairment; Inflammation; Inflammatory; Inflammatory Response; Injury; Intervention; Intravenous; Mediating; Natural regeneration; Neurologic Deficit; Patients; Pharmacologic Substance; Pharmacological Treatment; Physiological; Play; Population; Property; Quality of life; Recovery; Recovery of Function; Research; Role; Site; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Spleen; Staging; Therapeutic; Tissues; Triage; acute care; design; improved; inflammatory modulation; injured; innovation; intravenous administration; loss of function; male; nanoparticle; programs; response; severe injury; sex; trafficking

Traumatic spinal cord injury (SCI) leads to primary injury, followed by secondary injuries including inflammation which create an inhibitory environment. Regeneration is limited due to additional tissue damages and an inhibitory environment, leading to various neurological deficits. The goal of this proposal is to develop a non-invasive acute intervention with the goal of modulating inflammatory responses to reprogram an inhibitory environment after SCI. Particularly, the SCI demographic shifts toward a more equal balance among males and females, indicating that improved therapeutics are needed since the difference in physiological factors between sexes play important roles in pharmacological treatments and functional recovery after SCI. In this study, Poly(lactide-co-glycolide) (PLG)-based multiple nanoparticle (NP) formulations will be designed with various physicochemical factors to identity sex-specific key functionality of NPs to reprogram inflammation, thereby facilitating functional recovery in females and males respectively after SCI. Specific aim 1 will investigate NP-induced innate cells modulation following SCI to identify sex-specific key properties of NPs. The distinct physicochemical properties of NPs will differently limit inflammation after SCI. Specific aim 2 will assess NPs-mediated long-term dynamic responses in the spinal cord and their effects on anatomical and functional recovery in both sexes after SCI. Intravenously (IV) administered NPs will bind to pro-inflammatory subsets of immune populations and direct their trafficking to the spleen. NP-positive innate cells within the injured tissues will lead to a sustained response, facilitating an environment that improves recovery after SCI. Successful completion of proposed aims will provide efficient sex-specific NP designs to maximize functional recovery after SCI. In addition, NPs are made of FDA-approved material that enables NPs to be administered in triage or on site to patients diagnosed with SCI without direct intervention into the spinal cord. This study will provide a potentially practical therapy for the entire SCI population.

创伤性脊髓损伤(SCI)导致原发损伤，继发损伤包括炎症在内的继发性损伤产生抑制环境。由于额外的组织损伤和抑制环境，再生受到限制，导致各种神经缺陷。这项建议的目的是开发一种非侵入性的急性干预措施，目的是调节炎症反应，以重新规划脊髓损伤后的抑制环境。特别是，脊髓损伤的人口统计学特征趋向于男女之间更加平等的平衡，这表明需要改进的治疗方法，因为性别之间的生理因素差异在脊髓损伤后的药物治疗和功能恢复中发挥着重要作用。在这项研究中，基于聚丙交酯-乙交酯(PLG)(PLG)的多纳米颗粒(NP)制剂将设计包含各种物理化学因素的多纳米颗粒(NP)，以确定NPs的性别特异性关键功能，从而重新编程炎症，从而分别促进女性和男性脊髓损伤后的功能恢复。具体目标1将研究脊髓损伤后NP诱导的先天细胞的调节，以确定NPs的性别特异性关键特性。NPs独特的物理化学性质将不同程度地限制脊髓损伤后的炎症反应。具体目标2将评估脊髓损伤后NPs介导的脊髓长期动态反应及其对男女解剖和功能恢复的影响。静脉给药(IV)的NPs将与免疫群体的促炎亚群结合，并将其运输到脾。损伤组织内NP阳性的天然细胞将导致持续的反应，促进脊髓损伤后恢复的环境。成功完成拟议的AIMS将提供有效的针对性别的NP设计，以最大限度地促进脊髓损伤后的功能恢复。此外，NPs是由FDA批准的材料制成的，使NPs能够在分流或现场给药给被诊断为脊髓损伤的患者，而不需要直接干预脊髓。这项研究将为整个脊髓损伤人群提供一种潜在的实用治疗方法。