The effects of coating pDNA/chitosan complexes with chondroitin sulfate on physicochemical characteristics and cell transfection

Hagiwara, Kazuyoshi; Nakata, Mitsuhiro; Koyama, Yoshiyuki; Sato, Toshinori

doi:10.1016/j.biomaterials.2012.06.040

Cited by 46 publications

(34 citation statements)

References 44 publications

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“…Transfection efficiency of CS complex transiently decreased at charge ratio 4-8 but the effect equivalent to PAMAM dendriplex was shown by charge ratio >10. Hagiwara et al 20) reported that molecular weight of CS can affect transfection efficiency of complexes. Only commercial CS was used in the present study.…”

Section: Fig 7 In Vivo Gene Expression Of Each Complex Administeredmentioning

confidence: 99%

“…These results suggest that CS-coated particles were predominantly taken up by clathrin-mediated endocytosis. Hagiwara et al 20) however, showed that the complex formed by combining pDNA/chitosan complex and CS (pDNA/chitosan/CS complex, diameter 186.3 nm) was taken up by COS7 cells via macropinocytosis. These conflicting results may be explained by the different particle sizes.…”

Section: Fig 7 In Vivo Gene Expression Of Each Complex Administeredmentioning

confidence: 99%

“…17,18) Encapsulation of the cationic vector with anionic polymer was reported to show high transfection efficiency and safe vectors. 19,20) Among anionic polymers, chondroitin sulfate (CS) is highly biocompatible and has been used for tablets, eye drops, cosmetics, and medical applications. [21][22][23][24][25] Moreover, some reports have shown that CS has anti-inflammatory activities and anticancer activities.…”

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confidence: 99%

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Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

Imamura

Kodama

Higuchi

et al. 2014

Biological & Pharmaceutical Bulletin

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The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with polyamidoamine (PAMAM) dendrimer and chondroitin sulfate (CS) for effective and secure gene delivery. PAMAM dendrimers are new cationic polymers that are expected to be used as gene delivery vectors. However, cationic non-viral gene vectors showed cytotoxicity by binding to negative cellular membranes. We therefore prepared a ternary complex by adding CS, an anionic polymer, and examined its usefulness. The pDNA/PAMAM dendrimer complex (PAMAM dendriplex) and the PAMAM dendriplex coated by CS (CS complex) showed nanoparticles with positive ζ-potential and negative ζ-potential, respectively. The CS complex had no cytotoxicity against B16-F10 cells and no agglutination activity, although severe cytotoxicity and high agglutination were observed in the PAMAM dendriplex. As a result of an in vitro gene expression study of B16-F10 cells, not only the PAMAM dendriplex but also the CS complex showed high transfection efficiency. The transfection efficiency of the CS complex was significantly inhibited by clathrinmediated endocytosis inhibitor (chlorpromazine), caveolae-mediated endocytosis inhibitor (genistein), and hypothermia. Tail-vein injection of the CS complex into mice led to significantly higher gene expression in the spleen than the PAMAM dendriplex. Thus, the ternary complex of pDNA electrostatically assembled with PAMAM denriplex and CS showed safe high gene expression in the spleen. This vector is expected to be useful for useful gene delivery.Key words ternary complex; chondroitin sulfate; polyamidoamine dendrimer; gene delivery Gene therapy is expected to be an effective method to treat cancer, infection, innate immunodeficiency and cardiovascular diseases.1-4) The success of gene therapy is largely dependent on the development of vectors capable of effectively delivering foreign genes into targeted cells. One major approach in gene therapy is based on cationic polymers, such as polyethylenimine (PEI), polylysine, polyarginine, and chitosan.5-8) When cationic polymer-encapsulated plasmid DNA (pDNA) makes association with the cell surface, it enters the cells by endocytosis.Polyamidoamine (PAMAM) dendrimers are new cationic polymers, which are highly branched radial polymers that have specific and systematically variable size, shape and chemical structure. Their radical structure contains a 2-carbon ethylenediamine core and primary amino groups on the surface. Successive generations (G) have increasing diameter and double the surface functional amino groups of the preceding generation.9,10) PAMAM dendrimers can be used as carriers for pDNA and show high transfection efficiency. 11,12)The pDNA/PAMAM dendrimer complexes (PAMAM dendriplex) are formed by electrostatic interactions and initiate cell entry through binding to anionic phospholipids on the cell membrane. With increasing generations of dendrimers, the PAMAM dendriplex showed higher transfection efficiency, which depended on the charge rati...

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Section: Fig 7 In Vivo Gene Expression Of Each Complex Administeredmentioning

confidence: 99%

Section: Fig 7 In Vivo Gene Expression Of Each Complex Administeredmentioning

confidence: 99%

mentioning

confidence: 99%

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Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

Imamura

Kodama

Higuchi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…The vulnerability of DNA toward nuclease is one of the principal obstacles for efficient gene delivery in vitro and in vivo (Hagiwara et al, 2012). An efficient gene delivery system must be able to protect DNA from degradation by cellular nucleases.…”

Section: Gel Retardation and Resistance To Nuclease Assaymentioning

confidence: 99%

A novel potential biocompatible hyperbranched polyspermine for efficient lung cancer gene therapy

Xie

Jang

Liu

et al. 2015

International Journal of Pharmaceutics

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“…Kurosaki et al reported that ternary complexes of encapsulated poly-L-arginine or poly-L-lysine polyplexes ( Figure 5A) and DOTMA/Chol or DOTMA/DOPE lipoplexes of pDNA ( Figure 3A) with CS showed high transgene expression in B16-F10 cells with low cytotoxicity and low agglutination with erythrocytes [59]. Furthermore, Hagiwara et al reported that a ternary complex of pDNA/chitosan/CS ( Figure 5A) exhibited high cellular uptake via micropinocytosis [60], and strongly inhibited tumor growth in Huh-7 tumor xenografts by intratumoral injection of the complexes with pDNA encoding herpes simplex virus thymidine kinase (HSV-tk) [61]. Hamada et al reported that intraperitoneal injection of ternary complex ( Figure 5A) of pDNA/PEI/CS encoding murine granulocyte macrophage-colony- stimulating factor (mGM-CSF) prolonged survival in an intraperitoneal ovarian tumor model [62].…”

Section: Lo Et Al Reported That Cs-modi Ied Pei/pdna (mentioning

confidence: 99%

Progress in the development of Lipoplex and Polyplex modified with Anionic Polymer for efficient Gene Delivery

Hattori¹

2017

J Genet Med Gene Ther

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Nucleic acid-based therapy has become an increasingly important strategy for treating a variety of human diseases. In systemic therapy, a therapeutic gene must be delivered effi ciently to its target tissues without side effects. To deliver a therapeutic gene such as plasmid DNA (pDNA) or small interfering RNA (siRNA) to target tissues by systemic administration, cationic carriers such as cationic liposomes and polymers have been commonly used as a non-viral vector. However, the binary complex of therapeutic gene and cationic carrier must be stabilized in the blood circulation by avoiding agglutination with blood components, because electrostatic interactions between positively charged complexes and negatively charged erythrocytes can cause agglutination, and the agglutinates contribute to high entrapment of the therapeutic genes in the highly extended lung capillaries. One promising approach for overcoming this problem is modifi cation of the surface of cationic complexes with anionic biodegradable polymers such as hyaluronic acid, chondroitin sulfate, or polyglutamic acid. As another approach, we recently developed a sequential injection method of anionic polymer and cationic liposome/therapeutic gene complex (cationic lipoplex) for delivery of a therapeutic gene into the liver or liver metastasis. In this review, we describe recent advances in the delivery of therapeutic genes by lipid-and polymerbased carrier systems using anionic polymers.

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The effects of coating pDNA/chitosan complexes with chondroitin sulfate on physicochemical characteristics and cell transfection

Cited by 46 publications

References 44 publications

Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery

A novel potential biocompatible hyperbranched polyspermine for efficient lung cancer gene therapy

Progress in the development of Lipoplex and Polyplex modified with Anionic Polymer for efficient Gene Delivery

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