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

Li H, Liu Y, Chen L, Liu Q, Qi S, Cheng X, Lee YB, Ahn CH, Kim DJ, Lee RJ
J Drug Target 26 466-473 06/01/2018


BACKGROUND: RX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently in clinical trial for metastatic renal cancer.

PURPOSE: To improve the delivery of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).

METHODS: 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.

RESULTS: 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 IC

CONCLUSIONS: F-LAN-RX-0201 showed promise as a therapeutic agent for tumours with elevated folate-receptor expression.

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