Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting

Jiang, Hu‐Lin; Kwon, Jung-Taek; Kim, Eun‐Mi; Kim, You-Kyoung; Jere, Dhananjay; Jeong, Hwan-Jeong; Jang, Mi-Kyeong; Nah, Jae‐Woon; Xu, Cheng-Xiong; Park, In Kyu; Cho, Myung‐Haing; Cho, Chong‐Su

doi:10.1016/j.jconrel.2008.07.029

Cited by 141 publications

(81 citation statements)

References 29 publications

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“…Particle size is a particularly important factor that influences the access and passage of complexes at the targeted site. 12,15 As shown in Figure 2C, all complexes measured less than 75 nm, and the particle sizes tended to decrease with an increase in the N/P ratio (from 7 to 35). The relatively homogenous size distributions of the complexes, as measured by dynamic light scattering, were unimodal ( Figure 2D).…”

Section: Characterization Of Fpcp-dna Complexesmentioning

confidence: 80%

“…4,5 However, this system is significantly limited by the low transfection efficiency and low cell specificity of chitosans. 6 To address these limitations, several ligands, such as chitosan modified by folate, 6,7 transferrin, 8 mannose, 9,10 and galactose, 11,12 have been designed and evaluated for receptormediated endocytotic gene delivery. Of these, folate chitosans have been reported as cancer cell-targeting gene carriers because of specific ligand-receptor interactions between folate moieties and the folate receptor, which are absent in most normal tissues at a high frequency, but are amplified in a variety of human cancers, including liver cancer.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer

Kim

Minai-Tehrani²,

Lee³

et al. 2013

IJN

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Background: Chitosan and chitosan derivatives have been proposed as alternative and biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan is an aspect of this approach that must be addressed prior to any clinical application. In the present study, folated poly(ethylene glycol)-chitosan-graftpolyethylenimine (FPCP) was investigated as a potential folate receptor-overexpressed cancer cell targeting gene carrier. Methods: The FPCP copolymer was synthesized in two steps. In the first step, folate-PEG was synthesized by an amide formation reaction between the activated carboxyl groups of folic acid and the amine groups of bifunctional poly(ethylene glycol) (PEG). In the second step, FPCP was synthesized by an amide formation reaction between the activated carboxyl groups of folate-PEG and amine groups of CHI-g-polyethyleneimine (PEI). The composition of FPCP was characterized by 1 H nuclear magnetic resonance. Results: FPCP showed low cytotoxicity in various cell lines, and FPCP-DNA complexes showed good cancer cell specificity as well as good transfection efficiency in the presence of serum. Further, FPCP-Pdcd4 complexes reduced tumor numbers and progression more effectively than PEI 25 kDa in H-ras12V liver cancer mice after intravenous administration. Conclusion: Our data suggest that FPCP, which has improved transfection efficiency and cancer cell specificity, may be useful in gene therapy for liver cancer.

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Section: Characterization Of Fpcp-dna Complexesmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer

Kim

Minai-Tehrani²,

Lee³

et al. 2013

IJN

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“…2 Conjugate. Copolymer synthesis procedure described by Jiang et al [18] with modifications was employed in the synthesis of the amino terminal CHT-g-PEI-PEG-NH 2 copolymer conjugate following an amide formation reaction between the activated carboxyl groups of NH 2 -PEG-COOH and the amine groups of CHT-g-PEI as previously described. Briefly, the carboxyl group of the bifunctional PEG (NH 2 -PEG-COOH) was activated using NHS/EDC chemistry for 15 minutes.…”

Section: Synthesis Of the Chi-g-pei Conjugatementioning

confidence: 99%

Design and Characterization of Endostatin-Loaded Nanoparticles for In Vitro Antiangiogenesis in Squamous Cell Carcinoma

Adeyemi

Choonara

Kumar

et al. 2017

Journal of Nanomaterials

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The aim of this study is to effectively enhance antitumor activities of endostatin by preparing polymeric nanocarriers. NMR and FT-IR spectra confirmed the successful grafting of the CHT-g-PEI and CHT-g-PEI-PEG-NH 2 conjugates. SEM micrographs confirmed the shape of endostatin-loaded nanoparticles to be spherical while both TEM and zeta size results showed nanoparticle's average size to be 100.6 nm having a positively charged surface with zeta potential of 7.95 mV. The concentrations of CHT and TPP as well as the changing pH conditions account for the increased swelling pattern of endostatin-loaded nanoparticles and influenced endostatin release in vitro. PEI increased the overall amine protonation while PEG aggravated endostatin encapsulation and release. Nanoparticles swell and release endostatin at acidic tumor pH of 6.8 compared to physiological pH of 7.4. The native CHT-g-PEI-PEG-NH 2 conjugate showed high cytocompatibility above 80% cell viability across tested formulations. Endostatin-loaded nanoparticles showed a significant reduction in cell viability across tested formulations, with 5.32% cell death at 125 g/mL and 13.36% at 250 g/mL following 24 hours' incubation period. Interestingly, more than a fourfold (61.68%) increment in cytotoxicity was observed at nanoparticle concentration of 1000 g/mL. It was concluded that CHT-g-PEI-PEG-NH 2 is an effective cargo for endostatin delivery with antiangiogenic effect in squamous cell carcinoma.

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“…Hela cells without ASGP-Rs served as the control. [26][27][28][29][30][31][32] Cells were seeded on a cover glass in a 24-well culture plate at a density of 7 × 10 4 cells per well. The cells were incubated for 24 hours to 50% confluence and then treated with free DOX and a variety of liposomal DOX formulations for 2 hours.…”

Section: Cellular Internalizationmentioning

confidence: 99%

Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo

Yan¹,

Zhang²,

Zhang³

et al. 2013

IJN

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For the purposes of obtaining a hepatocyte-selective drug delivery system, a novel tetravalent galactosylated diethylenetriaminepentaacetic acid-distearoyl phosphatidylethanolamine (4Gal-DTPA-DSPE) was synthesized. The chemical structure of 4Gal-DTPA-DSPE was confirmed by proton nuclear magnetic resonance and mass spectrometry. The four galactose-modified liposomes (4Gal-liposomes) were prepared by thin-film hydration method, then doxorubicin (DOX) was encapsulated into liposomes using an ammonium sulfate gradient loading method. The liposomal formulations with 4Gal-DTPA-DSPE were characterized by laser confocal scanning microscopy and flow cytometry analysis, and the results demonstrated that the 4Gal-liposomes facilitated the intracellular uptake of DOX into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of 4Gal-liposomes was higher than that of the conventional liposomes without the galactose. Additionally, pharmacokinetic experiments in rats revealed that the 4Gal-liposomes displayed slower clearance from the systemic circulation compared with conventional liposomes. The organ distributions in mice and the study on frozen sections of liver implied that the 4Gal-liposomes enhanced the intracellular uptake of DOX into hepatocytes and prolonged the circulation. Taken together, these results indicate that liposomes containing 4Gal-DTPA-DSPE have great potential as drug delivery carriers for hepatocyte-selective targeting.

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Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting

Cited by 141 publications

References 29 publications

Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer

Therapeutic efficiency of folated poly(ethylene glycol)-chitosan-graft-polyethylenimine-Pdcd4 complexes in H-ras12V mice with liver cancer

Design and Characterization of Endostatin-Loaded Nanoparticles for In Vitro Antiangiogenesis in Squamous Cell Carcinoma

Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo

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