Enhanced lysosome escape mediated by 1,2-dicarboxylic-cyclohexene anhydride-modified poly-L-lysine dendrimer as a gene delivery system

Publication date: Available online 6 February 2020Source: Asian Journal of Pharmaceutical SciencesAuthor(s): Jianmin Shen, Jing Chen, Jingbo Ma, Linlan Fan, Xiaoli Zhang, Ting Yue, Yaping Yan, Yuhang ZhangAbstractAntisense oligodeoxynucleotide (ASODN) can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing, in turn, plays antitumor therapeutic roles. In the study, a novel HIF-1α ASODN-loaded nanocomposite was formulated to efficiently deliver gene to the target RNA. The physicochemical properties of nanocomposite were characterized using TEM, FTIR, DLS and zeta potentials. The mean diameter of resulting GEL-DGL-FA-ASODN-DCA nanocomposite was about 170-192 nm, and according to the agarose gel retardation assay, the loading amount of ASODN accounted for 166.7 mg/g. The results of cellular uptake showed that the nanocomposite could specifically target to HepG2 and Hela cells. The cytotoxicity assay demonstrated that the toxicity of vectors was greatly reduced by using DCA to reversibly block the cationic DGL. The subcellular distribution images clearly displayed the lysosomal escape ability of the DCA-modified nanocomposite. In vitro exploration of molecular mechanism indicated that the GEL-DGL-FA-ASODN-DCA nanocomposite could inhibit mRNA expression and HIF-1α protein translation at different levels. In vivo optical images and quantitative assay testified that the GEL-DGL-FA-ASODN-DCA formulation accumu...
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research