A Dual Targeting Drug Delivery System for Penetrating Blood-Brain Barrier and Selectively Delivering siRNA to Neurons for Alzheimer's Disease Treatment

Current Pharmaceutical Biotechnology
Chi ZhangHouwen Lin

Abstract

Alzheimer's disease (AD) is one of most serious threats to human beings, however, the treatment is hindered by blood-brain barrier and poor intra-brain cell selectivity. In this study, we developed a novel dual targeting drug delivery system by modification of NL4 peptide and apolipoprotein A-I (ApoA-I) onto dendrimer particles that may efficiently deliver siRNA into neuron cells to down-regulate BACE1 and inhibit Aβ formation. The constructed ANNP/ siRNA was approximately 79.26 nm with a spherical structure and a zeta potential of 3.53 mV. At N/P ratio of 10, the siRNA could be completely packaged into particles to avoid degradation by RNAase. In vitro, the modification with ApoA-I considerably increased bEnd.3 cell uptake and NL-4 considerably increased PC12 cell uptake. As a result, ANNP/siRNA showed higher uptake in both the cells. In addition, ANNP/siRNA could efficiently penetrate through bEnd.3 monolayers, which was 2.4-fold higher than unmodified complexes. In PC12 cells, the ANNP/siRNA could escape from endosomes and transport into cytoplasm after 8 h incubation, resulting in 87.5% BACE1 gene knockdown capacity, which was better than PEI. Additionally, the particles showed low cytotoxicity to both bEnd.3 and PC12 cells...Continue Reading

Citations

Apr 14, 2019·The Journal of Gene Medicine·Shanshan Wang, Rongqin Huang
Jan 1, 2020·Current Gene Therapy·Luis María Vaschetto
Jul 4, 2020·Nanomedicine·Jesus Garcia-ChicaRosalia Rodriguez-Rodriguez
Dec 1, 2019·Biomolecules·Yuefei ZhuZhiqing Pang
Dec 15, 2020·Biomaterials Science·João ConniotJoão Conde
Nov 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yana ZorkinaVladimir Chekhonin
Feb 15, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yilan XuHeng Zhang

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