Multifunctional DNA Tetrahedron for Alzheimer’s Disease Mitochondria-Targeted Therapy by MicroRNA Regulation
Weiqun Li, Xin Peng, Xuecui Mei, Mingjie Dong, Yingchun Li, Haifeng Dong
Abstract
The principal hallmark of Alzheimer's disease (AD) is neuron mitochondrial dysfunction, whereas mitochondrial miRNAs potentially play important roles. Nevertheless, efficacious mitochondria organelle therapeutic agents for treatment and management of AD are highly advisable. Herein, we report a multifunctional DNA tetrahedron-based mitochondria-targeted therapeutic platform, termed tetrahedral DNA framework-based nanoparticles (TDFNs), which was modified with triphenylphosphine (TPP) for mitochondria-targeting, cholesterol (Chol) for crossing the central nervous system, and functional antisense oligonucleotide (ASO) for both AD diagnosis and gene silencing therapy. After injecting intravenously through the tail vein of 3 × Tg-AD model mice, TDFNs can both easily cross the blood brain barrier and accurately arrive at the mitochondria. The functional ASO could not only be detected via the fluorescence signal for diagnosis but also mediate the apoptosis pathway through knocking miRNA-34a down, leading to recovery of the neuron cells. The superior performance of TDFNs suggests the great potential in mitochondria organelle therapeutics.