Non-covalent complexes of folic acid and oleic acid conjugated polyethylenimine: An efficient vehicle for antisense oligonucleotide delivery.
Polyethylenimine (PEI) was conjugated to oleic acid (PEI-OA) and evaluated as a delivery agent for LOR-2501, an antisense oligonucleotide against ribonucleotide reductase R1 subunit. PEI-OA/LOR-2501 complexes were further coated with folic acid (FA/PEI-OA/LOR-2501) and evaluated in tumor cells. The level of cellular uptake of FA/PEI-OA/LOR-2501 was more than double that of PEI/LOR-2501 complexes, and was not affected by the expression level of folate receptor (FR) on the cell surface. Efficient delivery was seen in several cell lines. Furthermore, pathway specific cellular internalization inhibitors and markers were used to reveal the principal mechanism of cellular uptake. FA/PEI-OA/LOR-2501 significantly induced the downregulation of R1 mRNA and R1 protein. This novel formulation of FA/PEI-OA provides a reliable and highly efficient method for delivery of oligonucleotide and warrants further investigation.
College of Life Sciences, Jilin University, Changchun 130012, China.
Shuang
S
Yang
College of Life Sciences, Jilin University, Changchun 130012, China.
Xuewei
X
Yang
College of Life Sciences, Jilin University, Changchun 130012, China.
Yan
Y
Liu
College of Life Sciences, Jilin University, Changchun 130012, China.
Bin
B
Zheng
College of Life Sciences, Jilin University, Changchun 130012, China.
Lingjun
L
Meng
College of Life Sciences, Jilin University, Changchun 130012, China; College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Robert J
RJ
Lee
College of Life Sciences, Jilin University, Changchun 130012, China. Electronic address: xiejing@jlu.edu.cn.
Jing
J
Xie
College of Life Sciences, Jilin University, Changchun 130012, China; State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai 264000, China. Electronic address: tenglesheng@jlu.edu.cn.
Lesheng
L
Teng
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003600:Cytosol / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems; D058975:Folate Receptor 1 / Q000187:drug effects; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D019301:Oleic Acid / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis
D000970:Antineoplastic Agents; D058975:Folate Receptor 1; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D019301:Oleic Acid; D011094:Polyethyleneimine; D005492:Folic Acid
Folic acid; Non-covalent; Oleic acid; Oligonucleotide delivery; Pathway; Polyethylenimine (PEI)