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）导致了一次初级损伤，其次是炎症，包括炎症，从而产生抑制环境。由于额外的组织损害和抑制环境，再生受到限制，导致各种神经系统缺陷。该提案的目的是开发非侵入性急性干预措施，其目的是调节炎症反应以在SCI后重新编程抑制环境。特别是，SCI人口统计学朝着男性和女性之间的平衡更加平衡，这表明需要改善治疗剂，因为性别之间的生理因素差异在药理治疗中起着重要作用在药理治疗和SCI后的功能恢复中起着重要作用。在这项研究中，将设计基于多种纳米颗粒（NP）制剂的聚（乳酸 - 糖 - 糖苷）（PLG）配方，具有各种物理化学因素，用于NP的身份性别特异性关键功能，以重新编程炎症，从而分别促进SCI后女性和男性的功能恢复。特定的目标1将研究SCI后NP诱导的先天细胞调节，以识别NP的性别特异性关键特性。 NP的不同理化特性将在SCI后限制炎症。特定的目标2将评估脊髓中NPS介导的长期动态反应及其对SCI后两性的解剖和功能恢复的影响。静脉内（IV）施用的NP将与免疫种群的促炎性子集结合，并将其贩运引导到脾脏。损伤组织中的NP阳性先天细胞将导致持续的反应，从而促进了改善SCI后恢复的环境。成功完成拟议的目标将提供有效的特定性别NP设计，以最大程度地提高SCI后功能恢复。此外，NP是由FDA批准的材料制成的，可以在三叶叶中或现场对诊断为SCI的患者进行NP，而无需直接干预脊髓。这项研究将为整个SCI人群提供潜在的实用疗法。