It is difficult to carry out early diagnosis and treatment of Multiple sclerosis (MS) because of the complex pathogenesis elicited by diversified autoantigens. Monocytes play important roles in the process of MS, especially as most of the amplified inflammatory monocytes cross the BBB to promote neuron injury and recruit more immune cells to infiltrate the central nervous system (CNS). Here, we propose monocytes as an effective immunotherapy target for MS. We used High-density lipoprotein-mimicking peptide-phospholipid scaffold (HPPS) as a carrier to improve the bioavailability of curcumin. Curcumin-loaded HPPS (Cur-HPPS) were taken up specifically and efficiently by monocytes through the scavenger receptor class B type I (SR-B1) receptor. This delivery hindered inflammatory monocytes across the BBB in EAE mice, inhibited the proliferation of microglia, and restricted the infiltration of other effector immune cells, resulting in the reduction of EAE morbidity from 100% to 30%. It attributed to the immunomodulatory effect of Cur-HPPS on inflammatory monocytes, which inhibited NF-κB activation and downregulated the expression of adhesion- and migration-related molecules. Meanwhile, infiltrated monocytes in the CNS of EAE mice characterize early inflammation. Therefore, targeted modulation of monocytes with HPPS carrying therapeutic and/or imaging agents offers a novel strategy for MS diagnosis and treatment.

由于多种自身抗原引起的复杂发病机制，因此很难进行多发性硬化症（MS）的早期诊断和治疗。单核细胞在MS的过程中起重要作用，尤其是当大多数扩增的炎性单核细胞通过BBB促进神经元损伤并募集更多的免疫细胞渗入中枢神经系统（CNS）时。在这里，我们建议单核细胞作为MS的有效免疫治疗目标。我们使用高密度脂蛋白模拟肽-磷脂支架（HPPS）作为载体，以改善姜黄素的生物利用度。单核细胞通过I型清道夫受体（SR-B1）受体特异性地和有效地吸收了姜黄素负载的HPPS（Cur-HPPS）。这种递送阻碍了EAE小鼠整个BBB中的炎性单核细胞，抑制小胶质细胞的增殖，并限制其他效应免疫细胞的浸润，导致EAE发病率从100％降低到30％。它归因于Cur-HPPS对炎性单核细胞的免疫调节作用，该作用抑制了NF-κB活化并下调了粘附和迁移相关分子的表达。同时，EAE小鼠中枢神经系统中浸润的单核细胞是早期炎症的特征。因此，用携带治疗剂和/或显像剂的HPPS靶向调节单核细胞可为MS诊断和治疗提供新的策略。抑制NF-κB活化并下调粘附和迁移相关分子的表达。同时，EAE小鼠中枢神经系统中浸润的单核细胞是早期炎症的特征。因此，用携带治疗剂和/或显像剂的HPPS靶向调节单核细胞可为MS诊断和治疗提供新的策略。抑制NF-κB活化并下调粘附和迁移相关分子的表达。同时，EAE小鼠中枢神经系统中浸润的单核细胞是早期炎症的特征。因此，用携带治疗剂和/或显像剂的HPPS靶向调节单核细胞可为MS诊断和治疗提供新的策略。