RGD targeting hyaluronic acid coating system for PEI-PBLG polycation gene carriers

Huayu Tian; Lin Lin; Jie Chen; Xuesi Chen; Tae Gwan Park; Atsushi Maruyama

doi:10.1016/j.jconrel.2011.01.025

RGD targeting hyaluronic acid coating system for PEI-PBLG polycation gene carriers

Huayu Tian, Lin Lin, Jie Chen, Xuesi Chen, Tae Gwan Park, Atsushi Maruyama

Research output: Contribution to journal › Article › peer-review

130 Scopus citations

Abstract

Hyaluronic acid (HA), a natural anionic mucopolysaccharide, was used to coat polyethylenimine-poly(γ-benzyl L-glutamate)/DNA (PEI-PBLG/DNA) complexes. HA was further modified by introducing RGD peptide with grafting density of one RGD in every 1.9 HA repeating units. HA can coat the cationic surface of PEI-PBLG/DNA complexes without destroying them even at high weight ratio of HA/PEI-PBLG/DNA = 40/10/1. Coating the complexes by HA and HA-RGD caused lower surface charges and little bigger size than the naked PEI-PBLG/DNA. HA/PEI-PBLG/DNA has little lower transfection efficiency compared with naked PEI-PBLG/DNA, while the transfection efficiency of HA-RGD/PEI-PBLG/DNA is 9.7 times of HA/PEI-PBLG/DNA for the RGD target bonding affinity to the receptors on the cell surface. HA coating on PEI-PBLG/DNA reduced the electrostatic binding affinity to the cells while the RGD binding affinity for integrin on HeLa cells can not only compensate the reduced binding affinity but also enhance the affinity for HA-RGD/PEI-PBLG/DNA. RGD and RDG competition assay and lactate dehydrogenase (LDH) release studies further confirmed the specific target functions of RGD on HA. Cell viability measurements confirmed the high viability (above 70% viability) of the cells treated with HA-RGD and HA coated complex particles. These results would show that HA-RGD coated PEI-PBLG/DNA complexes have an attractive feature to a targeting in vivo non-viral gene delivery system.

Original language	English
Pages (from-to)	47-53
Number of pages	7
Journal	Journal of Controlled Release
Volume	155
Issue number	1
DOIs	https://doi.org/10.1016/j.jconrel.2011.01.025
State	Published - Oct 10 2011
Externally published	Yes

Funding

The authors are thankful to the National Natural Science Foundation of China ( 20604028 , 50873102 , 50903009 , 21074129 and key program no: 50733003 ), and the National Natural Science Foundation of China, A3 Foresight Program (20621140369) the Program of Scientific Development of Jilin Province ( 20090128 and 20096018 ) for financial support to this work.

Funders	Funder number
A3 Foresight Program	20621140369
Program of Scientific Development of Jilin Province	20096018, 20090128
National Natural Science Foundation of China	50903009, 20604028, 50733003, 50873102, 21074129

Keywords

Coating system
Gene carriers
Hyaluronic acid
RGD peptide
Targeting

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10.1016/j.jconrel.2011.01.025

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title = "RGD targeting hyaluronic acid coating system for PEI-PBLG polycation gene carriers",

abstract = "Hyaluronic acid (HA), a natural anionic mucopolysaccharide, was used to coat polyethylenimine-poly(γ-benzyl L-glutamate)/DNA (PEI-PBLG/DNA) complexes. HA was further modified by introducing RGD peptide with grafting density of one RGD in every 1.9 HA repeating units. HA can coat the cationic surface of PEI-PBLG/DNA complexes without destroying them even at high weight ratio of HA/PEI-PBLG/DNA = 40/10/1. Coating the complexes by HA and HA-RGD caused lower surface charges and little bigger size than the naked PEI-PBLG/DNA. HA/PEI-PBLG/DNA has little lower transfection efficiency compared with naked PEI-PBLG/DNA, while the transfection efficiency of HA-RGD/PEI-PBLG/DNA is 9.7 times of HA/PEI-PBLG/DNA for the RGD target bonding affinity to the receptors on the cell surface. HA coating on PEI-PBLG/DNA reduced the electrostatic binding affinity to the cells while the RGD binding affinity for integrin on HeLa cells can not only compensate the reduced binding affinity but also enhance the affinity for HA-RGD/PEI-PBLG/DNA. RGD and RDG competition assay and lactate dehydrogenase (LDH) release studies further confirmed the specific target functions of RGD on HA. Cell viability measurements confirmed the high viability (above 70% viability) of the cells treated with HA-RGD and HA coated complex particles. These results would show that HA-RGD coated PEI-PBLG/DNA complexes have an attractive feature to a targeting in vivo non-viral gene delivery system.",

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author = "Huayu Tian and Lin Lin and Jie Chen and Xuesi Chen and Park, {Tae Gwan} and Atsushi Maruyama",

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AU - Lin, Lin

AU - Chen, Jie

AU - Chen, Xuesi

AU - Park, Tae Gwan

AU - Maruyama, Atsushi

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AB - Hyaluronic acid (HA), a natural anionic mucopolysaccharide, was used to coat polyethylenimine-poly(γ-benzyl L-glutamate)/DNA (PEI-PBLG/DNA) complexes. HA was further modified by introducing RGD peptide with grafting density of one RGD in every 1.9 HA repeating units. HA can coat the cationic surface of PEI-PBLG/DNA complexes without destroying them even at high weight ratio of HA/PEI-PBLG/DNA = 40/10/1. Coating the complexes by HA and HA-RGD caused lower surface charges and little bigger size than the naked PEI-PBLG/DNA. HA/PEI-PBLG/DNA has little lower transfection efficiency compared with naked PEI-PBLG/DNA, while the transfection efficiency of HA-RGD/PEI-PBLG/DNA is 9.7 times of HA/PEI-PBLG/DNA for the RGD target bonding affinity to the receptors on the cell surface. HA coating on PEI-PBLG/DNA reduced the electrostatic binding affinity to the cells while the RGD binding affinity for integrin on HeLa cells can not only compensate the reduced binding affinity but also enhance the affinity for HA-RGD/PEI-PBLG/DNA. RGD and RDG competition assay and lactate dehydrogenase (LDH) release studies further confirmed the specific target functions of RGD on HA. Cell viability measurements confirmed the high viability (above 70% viability) of the cells treated with HA-RGD and HA coated complex particles. These results would show that HA-RGD coated PEI-PBLG/DNA complexes have an attractive feature to a targeting in vivo non-viral gene delivery system.

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JF - Journal of Controlled Release

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ER -

RGD targeting hyaluronic acid coating system for PEI-PBLG polycation gene carriers

Abstract

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Keywords

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