RT Journal Article SR Electronic T1 Delivery of Antisense Oligonucleotide LOR-2501 Using Transferrin-conjugated Polyethylenimine-based Lipid Nanoparticle JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1785 OP 1793 DO 10.21873/anticanres.13285 VO 39 IS 4 A1 BIN ZHENG A1 SHUANG YANG A1 QINGPING TIAN A1 YIN XIE A1 SHUQIU ZHANG A1 ROBERT J. LEE YR 2019 UL http://ar.iiarjournals.org/content/39/4/1785.abstract AB Background/Aim: Efficient delivery of antisense oligonucleotide (ASO) by nanoparticle vectors is critical for its clinical application. The aim of this study was to design and evaluate a novel ASO vector TPSH-LP consisting of a reduction-sensitive cationic polymer PEI-SS-HA (PSH), lipids and transferrin (Tf) as a targeting ligand. Materials and Methods: PSH was synthesized based on PEI 25 kDa. Nanoparticles containing PSH and Tf (TPSH-LP) were prepared and used to deliver an ASO LOR-2501 targeting ribonucleotide reductase R1. The physical and chemical properties of TPSH-LP and cellular uptake in HepG2 cells were studied. Results: TPSH-LP formed a complex with LOR-2501 (L-TPSH-LP) which showed suitable particle size (267.77±16.20 nm) and zeta potential (4.87±0.52 mV). TPSH-LP showed lower cytotoxicity and higher transfection efficiency than PEI 25 kDa in HepG2 cells. The addition of Tf enhanced the targeting and delivery efficiency of PSH-LP. TPSH-LP transported LOR-2501 and down-regulated the levels of R1 protein efficiently by 64.15%. Conclusion: Data demonstrated the potential utility of TPSH-LP for oligonucleotide delivery in cancer therapy.