In vitro cytotoxicity of macromolecules in different cell culture systems

Choksakulnimitr, Suthummar; Masuda, Sada; Tokuda, Hideaki; Takakura, Yoshinobu; Hashida, Mitsuru

doi:10.1016/0168-3659(95)00007-u

Cited by 324 publications

(215 citation statements)

References 31 publications

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…Although an attractive alternative, and despite more than 20 years of research and development, lack of clinically measurable success using polymeric non-viral vectors has diminished credibility of this approach. Such synthetic vectors often show poor transfection efficiency coupled with transient gene expression [3,4]. They can display an unfavourable pharmacokinetic profile with high levels of liver/lung capture [5,6] and many have unacceptably toxicity [4,7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Such synthetic vectors often show poor transfection efficiency coupled with transient gene expression [3,4]. They can display an unfavourable pharmacokinetic profile with high levels of liver/lung capture [5,6] and many have unacceptably toxicity [4,7,8]. Moreover most polyplexes are ultimately impractical to manufacture on an industrial scale and/or use clinically.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Richardson

Pattrick

Lavignac

et al. 2010

Journal of Controlled Release

View full text Add to dashboard Cite

Linear poly(amidoamine)s (PAAs) have been designed to exhibit minimal non-specific toxicity, display pHdependent membrane lysis and deliver genes and toxins in vitro. The aim of this study was to measure PAA cellular uptake using ISA1-OG (and as a reference ISA23-OG) in B16F10 cells in vitro and, by subcellular fractionation, quantitate intracellular trafficking of 125 I-labelled ISA1-tyr in liver cells after intravenous (i.v.) administration to rats. The effect of time after administration (0.5-3 h) and ISA1 dose (0.04-100 mg/kg) on trafficking, and vesicle permeabilisation (N-acetyl-b-D-glucosaminidase (NAG) release from an isolated vesicular fraction) were also studied. ISA1-OG displayed~60-fold greater B16F10 cell uptake than ISA23-OG. Passage of ISA1 along the liver cell endocytic pathway caused a transient decrease in vesicle buoyant density (also visible by TEM). Increasing ISA1 dose from 10 mg/kg to 100 mg/kg increased both radioactivity and NAG levels in the cytosolic fraction (5-10 fold) at 1 h. Moreover, internalised ISA1 provoked NAG release from an isolated vesicular fraction in a dose-dependent manner. These results provide direct evidence, for the first time, of PAA permeabilisation of endocytic vesicular membranes in vivo, and they have important implications for potential efficacy/toxicity of such polymeric vectors.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Richardson

Pattrick

Lavignac

et al. 2010

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…Fukushima et al 13) reported that the intercalation rate of EB within DNA/lipid films was influenced by the hydrophobicity of DNA/lipid films and 18) reported that quaternary chitosan derivatives retained their electrical properties. However, polycationic materials are generally known to exhibit cytotoxicity in cell cultures 19,20) . Therefore, in the present study, primary ammonium salts were used to synthesize lipids for reducing the cationic property of DNA film -as it was done previously in a series of studies related to DNA/lipid complexes 1,2,13) .…”

Section: Discussionmentioning

confidence: 99%

Drug Binding and Releasing Characteristics of DNA/Lipid/PLGA Film

et al. 2007

View full text Add to dashboard Cite

We evaluated the blended compound of DNA/lipid complexes and PLGA (poly(D,L-lactide-co-glycolide)) as a carrier material for drug delivery system (DDS). Transparent, self-standing DNA/lipid/PLGA films were prepared by casting from an organic solvent such as DMSO/chloroform. Daunorubicin hydrochloride (DH) could intercalate and groove bind into DNA in the films, whereby the amount of DH bound to the films was controlled by the latter' s immersion period in DH aqueous solution. DH was released from DH films after immersion in PBS solution, whereby release rate was dependent on the chemical structure of lipids. Released DH caused reduction of cell viability during the cell culture of L929 mouse fibroblasts. These results suggested that DNA/lipid/PLGA film was a promising useful material for DDS.

show abstract

“…The PMMA-PEI nanocarrier is spherical in shape, monodisperse in aqueous medium and has a well-defined core-shell nanostructure with a highly extended PEI shell in water. The particle design is based on two main rationales: (1) to reduce PEI cytotoxicity through immobilizing the PEI molecules onto solid particles since the PEI toxicity is caused by the multiple attachment of cationic PEI onto the cell surface [27]; (2) to reduce the amount of PEI needed to form complex nanoparticles with DNA molecules through using preformed uniform core-shell nanoparticles containing PEI shells. Our previous results have demonstrated that this new type of PEI-based core-shell nanoparticles could effectively condense nucleic acids and protect them against enzymatic degradation.…”

Section: Introductionmentioning

confidence: 99%

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

Siu

Leung

et al. 2012

Biointerphases

View full text Add to dashboard Cite

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.

show abstract

In vitro cytotoxicity of macromolecules in different cell culture systems

Cited by 324 publications

References 31 publications

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Drug Binding and Releasing Characteristics of DNA/Lipid/PLGA Film

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

Contact Info

Product

Resources

About