CD38靶向共载USPIO/辛伐他汀的多功能脂质体对动脉硬化不稳定斑块的诊疗一体化实验研究

动脉硬化（AS）不稳定斑块的有效诊断与逆转是最大限度避免心血管事件的关键。研究证实M1型巨噬细胞在斑块破裂及炎性发展中扮演至关重要的角色，而CD38为其特异性靶点。辛伐他汀被验证具有体外诱导M1型巨噬细胞向抗炎性M2型极化的作用，体内有望促使斑块稳定。由此，我们在前一课题——AS靶向探针研究的基础上，构建共载MRI对比剂USPIO和辛伐他汀的纳米脂质体，并通过CD38单克隆抗体进行修饰，形成靶向不稳定斑块的多功能脂质体CD38-US-Lip。本研究将测定该纳米载体的性质表征，并从细胞水平和AS动物模型两个层面，评价其对不稳定斑块的影像监测和极化逆转作用，探讨其作用机制。本研究率先将不稳定斑块中M1型巨噬细胞的靶向造影与极化治疗相结合，综合运用分子影像学、纳米技术及免疫调节等手段，以期实现对AS不稳定斑块的诊断、早期治疗和实时监测作用。项目的实施还可能为其他炎性疾病的临床诊疗提供一种有效策略

Effective diagnosis and reversal of unstable arteriosclerosis plaque is most important to avoid cardiovascular events. Researches confirm that M1 macrophages play a crucial role in the plaque rupture and inflammatory development, CD38 as its specific targets. It has been verified: Simvastatin induces macrophage polarization towards an anti-inflammatory M2 phenotype in vitro, is expected to promote stabilization of unstable plaque in vivo. On the basis of our previous AS-targeted probe study, we intend to fabricate MRI contrast agents USPIO & simvastatin co-delivered multi-functional liposome CD38-US-Lip, which linked with CD38 monoclonal antibody for targeting unstable plaque. In this study, we would determine characterization of CD38-US-Lip, also evaluate its effect and mechanism on image monitoring and inducing polarization of unstable plaque in vitro and vivo. This study would be the first to discuss targeted contrast and treatment of M1 macrophages in unstable plaque by integrated means of molecular imaging, nanotechnology and immunoregulation, in order to fulfill AS diagnosis and treatment. Implementation of the subject might also provide an effective strategy for the clinical diagnosis and treatment of other inflammatory diseases.