Amyloid β (Aβ) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD). It has been previously shown that curcumin targets Aβ plaques and interferes with their formation, suggesting a potential role for prevention or treatment of AD. In the present invention, curcumin-derivatives with improved physicochemical properties were synthesized and a "click chemistry" as well as a conventional liposome preparation method, were used to generate nanoliposomes decorated with the curcumin derivatives. These derivatives were designed to maintain the planar structure required for interaction with Aβ, as directly confirmed by Surface Plasmon Resonance experiments. Surface Plasmon Resonance experiments, measuring the binding of flowing liposomes to immobilized Aβ1-42, indicated that the liposomes exposing curcumin derivatives have extremely high affinity for Aβ1-42 fibrils (1-5 nM), likely because of the occurrence of multivalent interactions. The present invention describes the synthesis of the curcumin derivatives and the preparation and characterization of new nanoliposomes with a very high affinity for Aβ1-42 fibrils, to be exploited as vectors for the targeted delivery of new diagnostic and therapeutic molecules for AD.
淀粉样蛋白β(Aβ)聚集物被认为是治疗和/或诊断阿尔茨海默病(AD)的可能靶点。先前已经显示
姜黄素靶向Aβ斑块并干扰其形成,暗示了其在预防或治疗AD中的潜在作用。在本发明中,合成了具有改进的物理
化学性质的
姜黄素衍
生物,并使用“点击
化学”以及传统的脂质体制备方法,生成了装饰有
姜黄素衍
生物的纳米脂质体。这些衍
生物被设计为保持与Aβ相互作用所需的平面结构,直接通过表面等离子共振实验证实。通过测量流动脂质体与固定的Aβ1-42的结合,表面等离子共振实验证明,暴露
姜黄素衍
生物的脂质体对Aβ1-42纤维具有极高的亲和力(1-5 nM),可能是由于多价相互作用的发生。本发明描述了
姜黄素衍
生物的合成以及具有极高亲和力的新型纳米脂质体的制备和表征,可作为用于靶向传递新的AD诊断和治疗分子的载体。