Abstract
Our previous studies have successfully grafted biotin and galactose onto chitosan (CS) and synthesized biotin modified galactosylated chitosan (Bio-GC). The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1. At this N/P ratio, the transfection efficiency in the hepatoma cells was the highest with a slow release effect. Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation, and can target the transfection into hepatoma cells by combination with galactose and biotin receptors. The transfection rate was inhibited by the competition of galactose and biotin. Bio-GC nanomaterials were imported into cells’ cytoplasm by their receptors, followed by the imported exogenous gene transfected into the cells. Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice, by carrying the gene through the blood to the hepatoma tissue. Taken together, bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation, improving the rate of transfection in hepatoma cells, and transporting the gene into the cytoplasm in vitro and in vivo. Therefore, they are efficient hepatoma-targeting gene carriers.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Tomanin R, Scarpa M. Why do We Need New Gene Therapy Viral Vectors? Characteristics, limitations and Future Perspectives of Viral Vector Transduction[J]. Curr. Gene Ther., 2004, 4: 357–372
Rybniker J, Nowag A, Janicki H, et al. Incorporation of Antigens into Viral Capsids Augments Immunogenicity of Adeno-associated Virus Vector-based Vaccines[J]. J. Virol., 2012, 86: 13 800–13 804
Wang HY, Sun YX, Deng JZ, et al. Effect of Peptides and Their Introduction Methods on Target Gene Transfer of Gene Vector Based on Disulfide-containing Polyethyleneimine[J]. Int. J. Pharm., 2012, 438: 191–201
Ma Z, Yang C, Song W, et al. Chitosan Hydrogel as siRNA Vector for Prolonged Gene Silencing[J]. J. Nanobiotechnology, 2014, 12: 23
Zhong H, Lei X, Qin L, et al. Augmentation of Adenovirus 5 Vector-mediated Gene Transduction under Physiological pH Conditions by a Chitosan/NaHCO3 Solution[J]. Gene Ther., 2011, 18: 232–239
Zhang X, Yao J, Zhang L, et al. Synthesis and Characterization of PEG-conjugated Quaternized Chitosan and Its Application as a Gene Vector[J]. Carbohydr. Polym., 2014, 103: 566–572
Sum CH, Wettig S, Slavcev RA. Impact of DNA Vector Topology on Non-viral Gene Therapeutic Safety and Efficacy[J]. Curr. Gene Ther., 2014, 14: 309–329
Vitor MT, Bergami-Santos PC, Barbuto JA, et al. Cationic Liposomes as Non-viral Vector for RNA Delivery in Cancer Immunotherapy[J]. Recent Pat. Drug Deliv. Formul., 2013, 7: 99–110
Peng SF, Tseng MT, Ho YC, et al. Mechanisms of Cellular Uptake and Intracellular Trafficking with Chitosan/DNA/poly(Gamma-glutamic Acid) Complexes as a Gene Delivery Vector[J]. Biomaterials, 2011, 32: 239–248
Wang X, Yao J, Zhou JP, et al. Synthesis and Evaluation of Chitosan-graft-polyethylenimine as a Gene Vector[J]. Pharmazie, 2010, 65(8): 572–579
Klausner EA, Zhang Z, Wong SP, et al. Corneal Gene Delivery: Chitosan Oligomer as a Carrier of CpG Rich, CpG Free or S/MAR Plasmid DNA[J]. J. Gene Med., 2012,14: 100–108
Cadete A, Figueiredo L, Lopes R, et al. Development and Characterization of a New Plasmid Delivery System Based on Chitosan-sodium Deoxycholate Nanoparticles[J]. Eur. J. Pharm. Sci., 2012,45: 451–458
Ahmed TA, Aljaeid BM. Preparation, Characterization, and Potential Application of Chitosan, Chitosan Derivatives, and Chitosan Metal Nanoparticles in Pharmaceutical Drug Delivery[J]. Drug Des. Devel. Ther., 2016, 10: 483–507
Rizeq BR, Younes NN, Rasool K, et al. Synthesis, Bioapplications, and Toxicity Evaluation of Chitosan-Based Nanoparticles[J]. Int. J. Mol. Sci., 2019, 20: 5 776
Cheng M, Han J, Li Q, et al. Synthesis of Galactosylated Chitosan/5-fluorouracil Nanoparticles and Its Characteristics, in vitro and in vivo Release Studies[J]. J. Biomed. Mater. Res. B Appl. Biomater., 2012,100: 2 035–2 043
Yang W, Cheng Y, Xu T, et al. Targeting Cancer Cells with Biotin-dendrimer Conjugates[J]. Eur. J. Med. Chem., 2009, 44: 862–868
Heo DN, Yang DH, Moon HJ, et al. Gold Nanoparticles Surface-functionalized with Paclitaxel Drug and Biotin Receptor as Theranostic Agents for Cancer Therapy[J]. Biomaterials, 2012, 33: 856–866
Cheng M, Ma D, Zhi K, et al. Synthesis of Biotin-Modified Galactosylated Chitosan Nanoparticles and Their Characteristics in Vitro and in Vivo[J]. Cell. Physiol. Biochem., 2018, 50(2): 569–584
Cheng M, Zhi K, Gao X, et al. Activation of Cellular Immunity and Marked Inhibition of Liver Cancer in a Mouse Model Following Gene Therapy and Tumor Expression of GM-SCF, IL-21, and Rae-1[J]. Mol. Cancer, 2013,12: 166
Yan CY, Gu JW, Hou DP, et al. Synthesis of Tat Tagged and Folate Modified N-succinyl-chitosan Self-assembly Nanoparticles as a Novel Gene Vector[J]. Int. J. Biol. Macromol., 2015, 72: 751–756
Cheng M, Chen H, Wang Y, et al. Optimized Synthesis of Glycyrrhetinic Acid-modified Chitosan 5-fluorouracil Nanoparticles and Their Characteristics[J]. Int. J. Nanomedicine, 2014, 9: 695–710
Huang M, Fong CW, Khor E, et al. Transfection Efficiency of Chitosan Vectors: Effect of Polymer Molecular Weight and Degree of Deacetylation[J]. J. Control Release, 2005, 106: 391–406
Romoren K, Pedersen S, Smistad G, et al. The influence of Formulation Variables on in Vitro Transfection Efficiency and Physicochemical Properties of Chitosan-based Polyplexes[J]. Int. J. Pharm., 2003, 261: 115–127
Huang M, Khor E, Lim LY. Uptake and Cytotoxicity of Chitosan Molecules and Nanoparticles: Effects of Molecular Weight and Degree of Deacetylation[J]. Pharm. Res., 2004, 21: 344–353
Zhao QQ, Chen JL, Lv TF, et al. N/P Ratio Significantly Influences the Transfection Efficiency and Cytotoxicity of a Polyethylenimine/Chitosan/DNA Complex[J]. Biol. Pharm. Bull., 2009, 32: 706–710
Cheng M, Li Q, Wan T, et al. Synthesis and Efficient Hepatocyte Targeting of Galactosylated Chitosan as a Gene Carrier in vitro and in vivo[J]. J. Biomed. Mater. Res. B Appl. Biomater., 2011, 99: 70–80
Dreher M R, Liu W, Michelich CR, et al. Tumor Vascular Permeability, Accumulation, and Penetration of Macromolecular Drug Carriers[J]. J. Natl. Cancer Inst., 2006, 98: 335–344
Goren D, Gabizon A, Barenholz Y. The Influence of Physical Characteristics of Liposomes Containing Doxorubicin on Their Pharmacological Behavior[J]. Biochim. Biophys. Acta, 1990, 1029: 285–294
Na DH, Murty SB, Lee KC, et al. Preparation and Stability of Poly(Ethylene Glycol) (PEG)Ylated Octreotide for Application to Microsphere Delivery[J]. AAPS Pharm. Sci. Tech., 2003, 4: E72
Liu W, Sun S, Cao Z, et al. An investigation on the Physicochemical Properties of Chitosan/DNA Polyelectrolyte Complexes[J]. Biomaterials, 2005, 26: 2 705–2 711
Artursson P, Lindmark T, Davis SS, et al. Effect of Chitosan on the Permeability of Monolayers of Intestinal Epithelial Cells (Caco-2)[J]. Pharm. Res., 1994, 11: 1 358–1 361
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
All authors declare that there are no competing interests.
Additional information
Funded by the Scientific Research Project of Shanghai Municipal Health Commission (No.201940430)
Rights and permissions
About this article
Cite this article
Cheng, M., Zhang, F., Li, Q. et al. Biotin-modified Galactosylated Chitosan-gene Carrier in Hepatoma Cells Targeting Delivery. J. Wuhan Univ. Technol.-Mat. Sci. Edit. 39, 522–531 (2024). https://doi.org/10.1007/s11595-024-2908-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11595-024-2908-4