DNA/polyethyleneimine/hyaluronic acid small complex particles and tumor suppression in mice

Ito, Tomoko; Yoshihara, Chieko; Hamada, Katsuyuki; Koyama, Yoshiyuki

doi:10.1016/j.biomaterials.2009.12.032

Cited by 87 publications

(69 citation statements)

References 23 publications

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“…On the other hand, we found that hyaluronic acid (HA) could be deposited onto DNA/polycation (or cationic lipid) complexes, markedly stabilizing their dispersion. [16][17][18] We then prepared a highly durable gene-expression system composed of injectable self-setting apatite cement with finely dispersed DNA/polycation/HA complex particles.…”

Section: Preparation Of Injectable Self-setting Apatite Cement and Apmentioning

confidence: 99%

Application of Calcium Phosphate as a Controlled-Release Device

Ito

Otsuka

2013

Biological & Pharmaceutical Bulletin

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Calcium phosphate (CaP)-based compounds are biocompatible and have been accepted as promising candidates for novel drug-releasing devices. CaP is biodegradable and can be utilized as a durable drug release reservoir. We developed an injectable self-setting apatite cement. When a plasmid DNA complex containing CaP was injected into tumor-bearing mice, it solidified in the body and slowly released the DNA complex, inducing durable gene expression and high therapeutic effect on solid tumors. Encapsulation of a drug by CaP acts as a protective capsule for the unstable contents and improves biocompatibility. CaP nanocapsules encapsulating a plasmid DNA complex or drug-involved micelle were prepared, and they showed high stability against enzyme and protein degradation. CaP also showed high potential as a durable acid pH buffer. Aqueous alginate solution was found to form a soft gel in the body and was investigated as a drug-releasing device. However, degradation of the alginate gel is sometimes too rapid in an acidic environment such as the area around osteoporotic bones. We found that amorphous CaP powder added to the alginate gel could control the dissociation rate, buffering the pH inside the gel. Alginate gel including CaP powder and a drug for osteoporosis allowed sustained release of the drug under acidic conditions, and a good therapeutic effect was achieved in osteoporosis model rats. CaP could thus be a valuable material for drug-delivery systems as a slow-releasing drug reservoir, a protective coating, or a pH buffer.

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Section: Preparation Of Injectable Self-setting Apatite Cement and Apmentioning

confidence: 99%

Application of Calcium Phosphate as a Controlled-Release Device

Ito

Otsuka

2013

Biological & Pharmaceutical Bulletin

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“…In vivo gene transfection 24,25 Male BALB/C mice, 4-5 weeks and weighing 18-22 g, were purchased from National Rodent Laboratory Animal Resources, Shanghai Branch (Shanghai, China), and maintained under specific pathogen-free condition for in vivo transfection study. All animal procedures were approved by the Committee for Animal Research of Shanghai Ocean University, China (SCXK (HU) 2007-0003) and carried out according to the Guide for the Care and Use of Laboratory Animals.…”

Section: Gene Transfection Efficiencymentioning

confidence: 99%

Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery

Liu¹,

Zhu²,

Wu³

et al. 2012

IJN

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Background: Chitosan shows particularly high biocompatibility and fairly low cytotoxicity. However, chitosan is insoluble at physiological pH. Moreover, it lacks charge, so shows poor transfection. In order to develop a new type of gene vector with high transfection efficiency and low cytotoxicity, amphiphilic chitosan was synthesized and linked with low-molecular weight polyethylenimine (PEI). Methods: We first synthesized amphiphilic chitosan -N-octyl-N-quatenary chitosan (OTMCS), then prepared degradable PEI derivates by cross-linking low-molecular weight PEI with amphiphilic chitosan to produce a new polymeric gene vector (OTMCS-PEI). The new gene vector was characterized by various physicochemical methods. We also determined its cytotoxicity and gene transfecton efficiency in vitro and in vivo. Results: The vector showed controlled degradation. It was very stable and showed excellent buffering capacity. The particle sizes of the OTMCS-PEI/DNA complexes were around 150-200 nm with proper zeta potentials from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 2.25 U DNase I/µg DNA. Furthermore, they were resistant to dissociation induced by 50% fetal bovine serum and 1100 µg/mL sodium heparin. OTMCS-PEI revealed lower cytotoxicity, even at higher doses. Compared with PEI 25 KDa, the OTMCS-PEI/DNA complexes also showed higher transfection efficiency in vitro and in vivo. Conclusion: OTMCS-PEI was a potential candidate as a safe and efficient gene vector for gene therapy.

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“…[15][16][17] In a previous study, we modified chitosan using hydrophobic stearic acid (SA) to form self-assembling micelles. It has been demonstrated that chitosan oligosaccharide (CSO)-SA micelles are not only a promising vehicle for antitumor drug delivery, 18,19 but are also effective gene carriers.…”

Section: Introductionmentioning

confidence: 99%

Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

Yao¹,

Du²,

Yuan³

et al. 2014

IJN

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Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA) micelles were synthesized in this study to improve the gene transfection efficiency of chitosan-g-stearic acid (CSO-SA). The CA-CSO-SA micelles had a similar size, critical micelle concentration, and morphology, but their zeta potential and cytotoxicity were reduced compared with CSO-SA micelles. After modification with cis-aconitate, the CA-CSO-SA micelles could also compact plasmid DNA (pDNA) to form nanocomplexes. However, the DNA binding ability of CA-CSO-SA was slightly reduced compared with that of CSO-SA. The transfection efficiency mediated by CA-CSO-SA/pDNA against HEK-293 cells reached up to 37%, and was much higher than that of CSO-SA/pDNA (16%). Although the cis-aconitate modification reduced cellular uptake kinetics in the initial stages, the total amount of cellular uptake tended to be the same after 24 hours of incubation. An endocytosis inhibition experiment showed that the internalization mechanism of CA-CSO-SA/pDNA in HEK-293 cells was mainly via clathrin-mediated endocytosis, as well as caveolae-mediated endocytosis and macropinocytosis. Observation of intracellular trafficking indicated that the CSO-SA/pDNA complexes were trapped in endolysosomes, but CA-CSO-SA/pDNA was more widely distributed in the cytosol. This study suggests that modification with cis-aconitate improves the transfection efficiency of CSO-SA/pDNA.

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DNA/polyethyleneimine/hyaluronic acid small complex particles and tumor suppression in mice

Cited by 87 publications

References 23 publications

Application of Calcium Phosphate as a Controlled-Release Device

Application of Calcium Phosphate as a Controlled-Release Device

Degradable copolymer based on amphiphilic N-octyl-N-quatenary chitosan and low-molecular weight polyethylenimine for gene delivery

Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

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