Bin Zheng1, Shuang Yang2, Qingping Tian1, Yin Xie1, Shuqiu Zhang3, Robert J Lee4,5. 1. School of Pharmacy, Shanxi Medical University, Taiyuan, P.R. China. 2. School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, P.R. China. 3. School of Pharmacy, Shanxi Medical University, Taiyuan, P.R. China lee.1339@osu.edu shuqiu.zhang@126.com. 4. College of Life Science, Jilin University, Changchun, P.R. China lee.1339@osu.edu shuqiu.zhang@126.com. 5. College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
Abstract
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. Copyright
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 ASOLOR-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. Copyright
Authors: Alexander Batista-Duharte; Luis Sendra; Maria José Herrero; Damiana Téllez-Martínez; Iracilda Zeppone Carlos; Salvador Francisco Aliño Journal: Biomolecules Date: 2020-02-17