Delivery of antisense oligonucleotide using polyethylenimine-based lipid nanoparticle modified with cell penetrating peptide

Drug Delivery

Dandan Wang¹  Yaojun Sun²  Shuang Yang²  Bin Zheng³ 

[1] Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China;School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China;School of Pharmacy, Shanxi Medical University, Taiyuan, Chin;

关键词: Polyethylenimine;    cell penetrating peptide;    lipid nanoparticles;    antisense oligonucleotide;    cancer;   

DOI  :  10.1080/10717544.2019.1667453

来源: publisher

【 摘 要 】

Efficient and stable delivery system of antisense oligonucleotide (ASO) is important and urgently needed. Here, an ASO delivery system, Lp-PPRP, which contains a cationic polymer based on PEI (branched, 25 kDa), named PEI-PC and a palmitic acid modified R8 (R8-PA) was prepared to deliver a kind of ASO, LOR-2501. The characteristics of the nanoparticles and the cellular uptake of LOR-2501 in HeLa cells and A549 cells were studied. Lp-PPRP showed suitable particle size and zeta potential to combine with LOR-2501; the particle size and zeta potential of Lp-PPRP/LOR were 276.87 ± 5.63 nm and 18.03 ± 0.25 mV. In vitro experiments suggested that Lp-PPRP had lower cytotoxic and higher transfection efficiency for delivering LOR-2501 compared with PEI. The addition of PEI-PC and R8-PA contributed to enhance the transfection efficiency of the nanoparticles. In HeLa cells and A549 cells, Lp-PPRP could transport LOR-2501 and down-regulate the level of R1 protein efficiently, and the R1 down regulations were 64.56% and 66.34%, respectively. Results suggested potential utility of Lp-PPRP in the development of ASO in tumor therapy.

【 授权许可】

CC BY