Zheng Bin, Yang Shuang, Tian Qingping, Xie Yin, Zhang Shuqiu, Lee Robert J
School of Pharmacy, Shanxi Medical University, Taiyuan, P.R. China.
School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, P.R. China.
Anticancer Res. 2019 Apr;39(4):1785-1793. doi: 10.21873/anticanres.13285.
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.
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.
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%.
Data demonstrated the potential utility of TPSH-LP for oligonucleotide delivery in cancer therapy.
背景/目的：通过纳米颗粒载体有效递送反义寡核苷酸（ASO）对其临床应用至关重要。本研究的目的是设计并评估一种新型ASO载体TPSH-LP，其由还原敏感型阳离子聚合物PEI-SS-HA（PSH）、脂质和作为靶向配体的转铁蛋白（Tf）组成。
基于25 kDa的PEI合成PSH。制备含有PSH和Tf的纳米颗粒（TPSH-LP），并用于递送靶向核糖核苷酸还原酶R1的ASO LOR-2501。研究了TPSH-LP的物理化学性质以及在HepG2细胞中的细胞摄取情况。
TPSH-LP与LOR-2501形成复合物（L-TPSH-LP），其粒径合适（267.77±16.20 nm），zeta电位为（4.87±0.52 mV）。在HepG2细胞中，TPSH-LP的细胞毒性低于25 kDa的PEI，转染效率更高。添加Tf提高了PSH-LP的靶向和递送效率。TPSH-LP转运LOR-2501并有效下调R1蛋白水平达64.15%。
数据证明了TPSH-LP在癌症治疗中用于寡核苷酸递送的潜在效用。
