Multidimensional successively targeted glucose-aptamer nano-system to achieve "Point-Surface" early intervention of...

Difficulties such as low blood-brain barrier (BBB) permeability, insufficient accumulation of lesions and late treatment stage lead to difficulties in the treatment of Alzheimer's disease (AD). In this paper, a successively targeted polydopamine nano-system (Apt@PDA-Glu) was prepared for the first two difficulties, and the high transmittance of BBB in the nano-system was achieved by glycemic control method and primary targeting ligand glucose (Glu). Further, by secondary targeting ligand aptamer (Apt) targeting the early biomarker AβO of AD to achieving high accumulation in the lesion site. In addition, the photothermal ability of PDA can be used to ablate AβO, a toxic marker in the early stage of AD, so as to achieve "Point" intervention, and the antioxidant and anti-inflammatory ability of PDA can improve the steady state of brain microenvironment in the early stage of AD and achieve "Surface" intervention effect. The fluorescence intensity of brain in vitro showed that Apt@PDA-Glu was 4.1 times higher than that of PDA group, and 2 times higher than that of other nanoparticles using PDA as carrier. According to the image, most of them gathered in the diseased hippocampus, indicating that the nano-system can achieve high accumulation in the diseased area. The results of brain immunofluorescence showed that Apt@PDA-Glu can effectively remove AβO from the brain, and it was closer to the normal level. The results further showed that the accumulation of nano-system at the lesion site was increased by secondary targeting ligands. This study finally realized multidimensional intervention of AD through successively targeting strategy and "Point-Surface" intervention of carrier PDA, which can provide new insights for improving the curative effect of AD.