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Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic delivery of an Akt1 antisense oligonucleotide

Authors :
Robert J. Lee
Chang-Ho Ahn
Deog Joong Kim
Young Bok Lee
Lihua Chen
Shan-Shan Qi
Qibing Liu
Yang Liu
Xinwei Cheng
Hong Li
Source :
Journal of Drug Targeting. 26:466-473
Publication Year :
2018
Publisher :
Informa UK Limited, 2018.

Abstract

RX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently in clinical trial for metastatic renal cancer.To improve the delivery of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).F-LAN were synthesized with the composition of DOTAP/soyPC/TPGS/folate-PEG-DSPE (25:70:4:1 m/m), a cationic human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate and RX-0201. The nanoparticles were evaluated in KB human carcinoma cells in vitro and in a KB murine xenograft tumour model in vivo for pharmacokinetics and antitumor activities.The F-LAN-RX-0201 had a mean particle size of 108.6 ± 5.8 nm, zeta potential of 10.5 ± 3.2 mV and ASO loading efficiency of 71.5 ± 4.5%. In KB cells, uptake and Akt1 inhibition by F-LAN-RX-0201 were greater than those of non-targeted LAN-RX-0201 and could be partially blocked by excess free folate. F-LAN-RX-0201 inhibited cell growth with an ICF-LAN-RX-0201 showed promise as a therapeutic agent for tumours with elevated folate-receptor expression.

Details

ISSN :
10292330 and 1061186X
Volume :
26
Database :
OpenAIRE
Journal :
Journal of Drug Targeting
Accession number :
edsair.doi.dedup.....8b5670b64738dcdefc4653ebe357ed77
Full Text :
https://doi.org/10.1080/1061186x.2018.1433678