Pluronic‐grafted poly‐(<scp>L</scp>)‐lysine as a new synthetic gene carrier

Jeon, Eun-Jung; Kim, Hee-Doo; Kim, Jinseok

doi:10.1002/jbm.a.10012

Cited by 55 publications

(32 citation statements)

References 29 publications

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“…Cationic polymers have also been used in conjuction with ampiphillic Pluronic® copolymers, which consist of poly-ethylene oxide (PEO) and poly-proplylene oxide (PPO) repeats. Conjugation of cationic polymers such as polyethylenimine or poly[2-dimethylamino ethyl methacrylate] (pDMAEMA) with Pluronic® copolymers has been shown to improve transfection efficiencies and decreased toxicity [119][120][121].…”

Section: Biocompatibility and Modifications To Reduce Toxicitymentioning

confidence: 99%

Rationally Designed Synthetic Vectors for Gene Delivery

Rao¹,

Yadava²,

Hughes³

2007

TODDJ

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Vector development is one of the most important challenges facing the successful use of genes for treatment of diseases. Although chemically produced vectors offer distinct advantages over biological systems such as viruses, there are still some hurdles that have to be overcome before synthetic gene delivery vectors can be successfully implemented. This brief review discusses the biological barriers that limit current delivery strategies and reviews currently employed strategies for plasmid delivery. Nanoparticle-based gene delivery is reviewed along with methods for their characterization, physiochemical properties and toxicity. Finally a prospectus is provided for future development of an ideal synthetic gene delivery vector.

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Section: Biocompatibility and Modifications To Reduce Toxicitymentioning

confidence: 99%

Rationally Designed Synthetic Vectors for Gene Delivery

Rao¹,

Yadava²,

Hughes³

2007

TODDJ

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“…They can self-assemble into micelles with a hydrophobic core by PPO and a hydrophilic shell by PEO. 17 The pluronic copolymers have been modified with cationic polymers, such as PEI, 18 PLL, 19 and PDMAEMA, [20][21][22] to improve gene transfection as well as to reduce cytotoxicity. The hydrophobic PPO segments of pluronic polymers enhance the stability of polyplexes between polymers and deoxyribonucleic acid (DNA), 23,24 and promote the cellular uptake of polyplexes because of the increased interaction between the cell membrane and polyplexes.…”

Section: Introductionmentioning

confidence: 99%

Pentablock copolymers of pluronic F127 and modified poly(2-dimethyl amino)ethyl methacrylate for internalization mechanism and gene transfection studies

Huang

Wang²,

Lue³

et al. 2013

IJN

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Cationic polymers are one of the major nonviral gene delivery vectors investigated in the past decade. In this study, we synthesized several cationic copolymers using atom transfer radical polymerization (ATRP) for gene delivery vectors: pluronic F127-poly(dimethylaminoethyl methacrylate) (PF127-pDMAEMA), pluronic F127-poly (dimethylaminoethyl methacrylatetert-butyl acrylate) (PF127-p(DMAEMA-tBA)), and pluronic F127-poly(dimethylaminoethyl methacrylate-acrylic acid) (PF127-p(DMAEMA-AA)). The copolymers showed high buffering capacity and efficiently complexed with plasmid deoxyribonucleic acid (pDNA) to form nanoparticles 80-180 nm in diameter and with positive zeta potentials. In the absence of 10% fetal bovine serum, PF127-p(DMAEMA-AA) showed the highest gene expression and the lowest cytotoxicity in 293T cells. After acrylic acid groups had been linked with a fluorescent dye, the confocal laser scanning microscopic image showed that PF127-p(DMAEMA-AA)/pDNA could efficiently enter the cells. Both clathrin-mediated and caveolae-mediated endocytosis mechanisms were involved. Our results showed that PF127-p(DMAEMA-AA) has great potential to be a gene delivery vector.

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“…However, their applications are seriously hampered by safety issues (i.e. the possibility of inducing severe immune responses, and the provocation of mutagenesis) [5][6][7], difficulty in their mass production and limitation in gene loading capacity [5]. In the last decade, synthetic nonviral vectors have been rapidly developed because of the advancement in polymer science and nanotechnology.…”

Section: Introductionmentioning

confidence: 99%

“…These non-viral vectors are considered as alternatives to overcome the adverse effects of viral vectors. Among the various types of non-viral vectors, cationic polymers such as polylysine (PLL) [6,7], polyethylenimine (PEI) [8][9][10][11], polyamidoamine dendrimer (PAMAM) [12][13][14][15] and chitosan [16][17][18] have received a great deal of attention owing to their advantageous properties as compared with the viral and cationic liposome-based vectors. For examples, they are easy to prepare and to be chemically modified.…”

Section: Introductionmentioning

confidence: 99%

Polyethylenimine-Based Amphiphilic Core–Shell Nanoparticles: Study of Gene Delivery and Intracellular Trafficking

Siu

Leung

et al. 2012

Biointerphases

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Amphiphilic core–shell nanoparticle, which is composed of a hydrophobic core and a branched polyethylenimine (PEI) shell, has been designed and synthesized as a novel gene delivery nanocarrier. In our previous study, we demonstrated that the core–shell nanoparticle was not only able to efficiently complex with plasmid DNA (pDNA) and protect it against enzymatic degradation, but also three times less cytotoxic, and threefold more efficient in gene transfection than branched 25 kDa PEI. This paper reports our further studies in the following three aspects: (1) the ability of the PEI-based nanoparticles to deliver gene in various mammalian cell lines; (2) intracellular distributions of the nanoparticles and their pDNA complexes in HeLa cells; and (3) incorporation of nuclear targeting agent into the nanoparticle/pDNA complexes to enhance the nuclear targeting ability. The PEI-based nanoparticles were able to transfect both human and non-human cell lines and their transfection efficiencies were cell-dependent. Within our four tested cell lines (MCF-7, BEL 7404, C6 and CHO-K1), gene transfer using PEI-based core–shell nanoparticles displayed gene expression levels comparable to, or even better than, the commercial Lipofectamine™ 2000. Confocal laser scanning microscopy showed that the nanoparticles and their pDNA complexes were effectively internalized into the HeLa cells. The in vitro time series experiments illustrated that both the nanoparticle/pDNA complexes and PEI-based nanoparticles were distributed in the cytoplasmic region after transfection for 10 and 60 min, respectively. Nuclear localization was also observed in both samples after transfection for 20 and 60 min, respectively. Incorporation of the high mobility group box 1 (HMGB1) protein for nuclear targeting has also been demonstrated with a simple approach: electrostatic complexation between the PEI-based nanoparticles and HMGB1. In the in vitro transfection study in MCF-7 cells, the expression level of the firefly luciferase gene encoded by the pDNA increased remarkably by up to eightfold when the HMGB1 protein was incorporated into the nanoparticle/pDNA complexes. Our results demonstrate that the PEI-based core–shell nanoparticles are promising nanocarriers for gene delivery.

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Pluronic‐grafted poly‐(L)‐lysine as a new synthetic gene carrier

Cited by 55 publications

References 29 publications

Rationally Designed Synthetic Vectors for Gene Delivery

Rationally Designed Synthetic Vectors for Gene Delivery

Pentablock copolymers of pluronic F127 and modified poly(2-dimethyl amino)ethyl methacrylate for internalization mechanism and gene transfection studies

Polyethylenimine-Based Amphiphilic Core–Shell Nanoparticles: Study of Gene Delivery and Intracellular Trafficking

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