Advances in the application of poly(ethylenimine) conjugated bio- reducible dendrimers for gene delivery systems
Main Article Content
Abstract
The bio-reducible dendrimers containing poly(ethylenimine) and disulfides are interested in gene delivery systems as carrier for gene therapy. The synthesis
and characterization of poly(ethylenimine) conjugated polymers has been reviewed for the development of gene delivery systems. The linear PEIs and branched PEIs of bio-reducible dendrimers have briefly introduced in this paper. The preparation and application of poly(ethylenimine)s conjugated bio-reducible dendrimers are also discussed for the discovery of gene delivery systems. The bio-reducible poly(ethylenimine)s dendrimers have a great potential as gene carriers in drug delivery systems. It has reported that the bio-reducible PEIs branched dendrimers have a great potential as a gene delivery system consisting of PEI (1.8kDa) with disulfide bonds.
Keywords:
Gene therapy, gene delivery system, bio-reducible dendrimer, poly(ethylenimine)(PEI), PEI-conjugated polymer
Article Details
How to Cite
SUNG, Yong Kiel; KIM, Sung Wan.
Advances in the application of poly(ethylenimine) conjugated bio- reducible dendrimers for gene delivery systems.
Medical Research Archives, [S.l.], v. 6, n. 12, dec. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1883>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v6i12.1883.
Section
Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Kim T, Kim SW. Bio-reducible polymers for gene delivery. Reac. Func. Polym. 2011; 71:344-349.
2. Nam K, Jung S, Nam J-P, Kim SW. Poly(ethylenimine) conjugated bio-reducible dendrimer for efficient gene delivery. J. Control. Rel. 2015; 220:447-455. doi: 10.1016/j.jconrel.2015.11.005.
3. Nam J-P, Kim S, Kim SW. Design of PEI-conjugated bio-reducible polymer for efficient gene delivery. Int. J. Pharm. 2018; 545(1-2):295-305. doi: 10.1016/j.ijpharm.2018.04.051.
4. Huang H, Yu H, Tang G, Wang Q, Li J. Low molecular weight polyethylenimine cross-linked by 2-hydroxypropyl-ɤ-cyclodextrin coupled to peptide targeting HER2 as a gene delivery vector. Biomaterials. 2010; 31:1830-1838.
5. Jia L, Li Z, Zhang D, Zhang Q, Shen J, Guo H, Tian X, Liu G, Zheng D, Qi L. Redox-responsive catiomer based on PEG-ss-chitosan oligosaccharide-ss-polyethylenimine copolymer for effective gene delivery. Polym. Chem. 2013; 4:156-165.
6. Gosselin MA, Guo W, Lee RJ. Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine. Bioconjug. Chem. 2001; 12:989-994.
7. Nam HY, Nam K, Hahn HJ, Kim BH, Lim HJ, Kim HJ, Choi JS, Park JS. Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity. Biomaterials. 2009; 30:665-673.
8. Ahn CH, Chae SY, Bae YH, Kim SW. Biodegradable poly(ethylenimine) for plasmid DNA delivery. J. Control. Rel. 2002; 80:273-282.
9. Kim TI, Ou M, Lee M, Kim SW, Arginine-grafted bio-reducible poly(di-sulfide amine) for gene delivery systems. Biomaterials. 2009; 30(4): 658-664.
10. Nam HY, Nam K, Lee M, Kim SW, Bull DA, Dendrimer type bio-reducible polymer for efficient gene delivery. J. Control. Rel. 2012; 160(3): 592-600.
11. Ou M, Wang XL, Xu R, Chang CW, Bull DA, Kim SW, Novel bio-degradable poly(disulfide amine)s for gene delivery with high efficiency and low cytotoxicity. Bioconjug. Chem. 2008; 19(3): 626-633
12. Sung YK, Nam JP, Kim S, Kim SW. Recent development of bio-reducible polymers for efficient gene delivery. J. Cancer Treat. Diagno. 2018; JCTD-18-1145 in press.
13. Luo D, Salzman WM. Synthetic DNA delivery systems. Nat. Biotechnol. 200; 18:33-37.
14. Liu F, Huang L, Development of non-viral vectors for systemic gene delivery. J. Control. Rel. 2002; 78: 259-266.
15. Vaer P, van der Aa LJ, Engbersen JFJ, Strom G, Schiffelers RM. Disulfide-Based Poly(amido amine)s for siRNA Delivery: Effects of Structure on siRNA Complexation, Cellular Uptake, Gene Silencing and Toxicity. Pharm. Res. 2011; 28(5): 1013-1022.
16. Jeong JH, Kim SW, Park TG, Molecular design of functional polymers for gene therapy. Prog. Polym. Sci. 2007; 32:1239-1274.
17. Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr J. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: poly(ethylenimine). Proc. Natl. Acad. Sci. USA. 1995; 92:7297–301.
18. Abdallah B, Hassan A, Benoist C, Goula D, Behr JP, Demeneix BA. A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: poly(ethylenimine). Hum. Gene Ther. 1996; 7:1947–54.
19. Boletta A, Benigni A, Lutz J, Remuzzi G, Soria MR, Monaco L. Nonviral gene delivery to the rat kidney with poly(ethylenimine). Hum. Gene Ther. 1997; 8:1243–51.
20. Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T. A novel non-viral vector for DNA delivery based on low molecular weight, branched poly(ethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm. Res. 1999; 16:1273–9.
21. Gosselin MA, Guo W, Lee RJ. Efficient Gene Transfer Using Reversibly Cross-Linked Low Molecular Weight Polyethylenimine. Bioconjug. Chem. 2001; 12: 989-994.
22. Jeong JH, Song SH, Lim DW, Lee H, Park TG. DNA transfection using linear poly(ethylenimine) prepared by controlled acid hydrolysis of poly(2-ethyl-2-oxazoline). J Control Rel. 2001; 73:391–399.
23. Thomas M, Lu JJ, Ge Q, Zhang C, Chen J, Klibanov AM. Full deacylation of poly(ethylenimine) dramatically boosts its gene delivery efficiency and specificity to mouse lung. Proc. Natl. Acad. Sci. USA 2005; 102:5679–84.
24. von Harpe A, Petersen H, Li Y, Kissel T. Characterization of commercially available and synthesized poly(ethylenimine)s for gene delivery. J Control Rel. 2000; 69:309–322.
25. Suh J, Paik HJ, Hwang BK. Ionization of poly(ethylenimine) and poly(allylamine) at various pHs. Bioorg. Chem. 1994; 22:318–27.
26. Brissault B, Kichler A, Guis C, Leborgne C, Danos O, Cheradame H. Synthesis of linear poly(ethylenimine) derivatives for DNA transfection. Bioconjug. Chem 2003; 14:581–587.
27. Kobayashi S, Hiroishi K, Tokunoh M, Saegusa T. Chelating properties of linear and branched poly(ethylenimine). Macrolecules. 1987; 20:1496-1500.
28. Kircheis R, Wightman L, Wagner E. Design and gene delivery activity of modified poly(ethylenimine). Adv. Drug Deliv. Rev. 2001; 53: 341-358.
29. Ogris M, Steinlein P, Kursa M, Mechtler K, Kircheis R, Wagner E. The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells. Gene Ther. 1998; 5:1425–33.
30. Oh YK, Suh D, Kim JM, Choi HG, Shin K, Ko JJ. Poly(ethylenimine)-mediated cellular uptake, nucleus trafficking and expression of cytokine plasmid DNA. Gene Ther. 2002; 9:1627–32.
31. Ferrari S, Moro E, Pettenazzo A, Behr JP, Zacchello F, Scarpa M. ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo. Gene Ther. 1997; 4:1100–6.
32. Wightman L, Kircheis R, Rossler V, Carotta S, Ruzicka R, Kursa M, Wagner E. Different behavior of branched and linear poly(ethylenimine) for gene delivery in vitro and in vivo. J. Gene Med. 2001; 3:362–72.
33. Gautam A, Densmore CL, Xu B, Waldrep JC. Enhanced gene expression in mouse lung after PEI–DNA aerosol delivery. Mol Ther. 2000; 2:63–70.
34. Shi L, Tang GP, Gao SJ, Ma YX, Liu BH, Li Y, et al. Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted poly(ethylenimine) led to prolonged transgene expression in the spinal cord. Gene Ther. 2003; 10:1179–88.
35. Gharwan H, Wightman L, Kircheis R, Wagner E, Zatloukal K. Nonviral gene transfer into fetal mouse livers (a comparison between the cationic polymer PEI and naked DNA). Gene Ther. 2003; 10:810–817.
36. Goula D, Remy JS, Erbacher P, Wasowicz M, Levi G, Abdallah B, et al. Size, diffusibility and transfection performance of linear PEI/DNA complexes in the mouse central nervous system. Gene Ther. 1998; 5:712–717.
37. Kwon OJ, Kang E, Choi JW, Kim SW, Yun CO. Therapeutic targeting of chitosan-PEG-folate–complexed oncolytic adenovirus for active and systemic cancer gene therapy. J. Control. Rel. 2013; 169(3): 257-65.
38. Nam JP, Nam K, Jung S, Nah JW, Kim SW. Evaluation of dendrimer type bio-reducible polymer as a siRNA delivery carrier for cancer therapy. J. Control. Rel. 2015; 209: 179-85.
39. Kim H, Nam K, Nam JP, Kim HS, Kim YM, Joo WS, Kim SW. VEGF therapeutic gene delivery using dendrimer type bio-reducible polymer into human mesenchymal stem cells (hMSCs). J Control. Rel. 2015; 220: 222-228.
40. Choi JW, Nam JP, Nam K, Lee YS, Yun CO, Kim SW. Oncolytic adenovirus coated with multi-degradable bio-reducible core-cross-linked poly(ethylenimine) for cancer gene therapy. Biomacromolecules. 2015; 16(7): 2132-43.
41. Lee YS, Choi JW, Oh JE, Yun CO, Kim SW. Human relaxin gene expression delivered by bio-reducible dendrimer polymer for post-infarct cardiac remodeling in rats. Biomaterials. 2016; 97: 164-75.
42. Yockman JW, Brumbach JH, Kim SW. Cleavable modifications to reducible poly(amido-ethylenimne)s to enhance nucleotide delivery. U.S. Patent Application Publication. No.: US2013/0149783 A1 (Jun.13, 2013), 1-8.
43. Kim HA, Nam K, Kim SW. Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing plasmid delivery. Biomaterials. 2014; 35(26): 7543-7552.
2. Nam K, Jung S, Nam J-P, Kim SW. Poly(ethylenimine) conjugated bio-reducible dendrimer for efficient gene delivery. J. Control. Rel. 2015; 220:447-455. doi: 10.1016/j.jconrel.2015.11.005.
3. Nam J-P, Kim S, Kim SW. Design of PEI-conjugated bio-reducible polymer for efficient gene delivery. Int. J. Pharm. 2018; 545(1-2):295-305. doi: 10.1016/j.ijpharm.2018.04.051.
4. Huang H, Yu H, Tang G, Wang Q, Li J. Low molecular weight polyethylenimine cross-linked by 2-hydroxypropyl-ɤ-cyclodextrin coupled to peptide targeting HER2 as a gene delivery vector. Biomaterials. 2010; 31:1830-1838.
5. Jia L, Li Z, Zhang D, Zhang Q, Shen J, Guo H, Tian X, Liu G, Zheng D, Qi L. Redox-responsive catiomer based on PEG-ss-chitosan oligosaccharide-ss-polyethylenimine copolymer for effective gene delivery. Polym. Chem. 2013; 4:156-165.
6. Gosselin MA, Guo W, Lee RJ. Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine. Bioconjug. Chem. 2001; 12:989-994.
7. Nam HY, Nam K, Hahn HJ, Kim BH, Lim HJ, Kim HJ, Choi JS, Park JS. Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity. Biomaterials. 2009; 30:665-673.
8. Ahn CH, Chae SY, Bae YH, Kim SW. Biodegradable poly(ethylenimine) for plasmid DNA delivery. J. Control. Rel. 2002; 80:273-282.
9. Kim TI, Ou M, Lee M, Kim SW, Arginine-grafted bio-reducible poly(di-sulfide amine) for gene delivery systems. Biomaterials. 2009; 30(4): 658-664.
10. Nam HY, Nam K, Lee M, Kim SW, Bull DA, Dendrimer type bio-reducible polymer for efficient gene delivery. J. Control. Rel. 2012; 160(3): 592-600.
11. Ou M, Wang XL, Xu R, Chang CW, Bull DA, Kim SW, Novel bio-degradable poly(disulfide amine)s for gene delivery with high efficiency and low cytotoxicity. Bioconjug. Chem. 2008; 19(3): 626-633
12. Sung YK, Nam JP, Kim S, Kim SW. Recent development of bio-reducible polymers for efficient gene delivery. J. Cancer Treat. Diagno. 2018; JCTD-18-1145 in press.
13. Luo D, Salzman WM. Synthetic DNA delivery systems. Nat. Biotechnol. 200; 18:33-37.
14. Liu F, Huang L, Development of non-viral vectors for systemic gene delivery. J. Control. Rel. 2002; 78: 259-266.
15. Vaer P, van der Aa LJ, Engbersen JFJ, Strom G, Schiffelers RM. Disulfide-Based Poly(amido amine)s for siRNA Delivery: Effects of Structure on siRNA Complexation, Cellular Uptake, Gene Silencing and Toxicity. Pharm. Res. 2011; 28(5): 1013-1022.
16. Jeong JH, Kim SW, Park TG, Molecular design of functional polymers for gene therapy. Prog. Polym. Sci. 2007; 32:1239-1274.
17. Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr J. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: poly(ethylenimine). Proc. Natl. Acad. Sci. USA. 1995; 92:7297–301.
18. Abdallah B, Hassan A, Benoist C, Goula D, Behr JP, Demeneix BA. A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: poly(ethylenimine). Hum. Gene Ther. 1996; 7:1947–54.
19. Boletta A, Benigni A, Lutz J, Remuzzi G, Soria MR, Monaco L. Nonviral gene delivery to the rat kidney with poly(ethylenimine). Hum. Gene Ther. 1997; 8:1243–51.
20. Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T. A novel non-viral vector for DNA delivery based on low molecular weight, branched poly(ethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm. Res. 1999; 16:1273–9.
21. Gosselin MA, Guo W, Lee RJ. Efficient Gene Transfer Using Reversibly Cross-Linked Low Molecular Weight Polyethylenimine. Bioconjug. Chem. 2001; 12: 989-994.
22. Jeong JH, Song SH, Lim DW, Lee H, Park TG. DNA transfection using linear poly(ethylenimine) prepared by controlled acid hydrolysis of poly(2-ethyl-2-oxazoline). J Control Rel. 2001; 73:391–399.
23. Thomas M, Lu JJ, Ge Q, Zhang C, Chen J, Klibanov AM. Full deacylation of poly(ethylenimine) dramatically boosts its gene delivery efficiency and specificity to mouse lung. Proc. Natl. Acad. Sci. USA 2005; 102:5679–84.
24. von Harpe A, Petersen H, Li Y, Kissel T. Characterization of commercially available and synthesized poly(ethylenimine)s for gene delivery. J Control Rel. 2000; 69:309–322.
25. Suh J, Paik HJ, Hwang BK. Ionization of poly(ethylenimine) and poly(allylamine) at various pHs. Bioorg. Chem. 1994; 22:318–27.
26. Brissault B, Kichler A, Guis C, Leborgne C, Danos O, Cheradame H. Synthesis of linear poly(ethylenimine) derivatives for DNA transfection. Bioconjug. Chem 2003; 14:581–587.
27. Kobayashi S, Hiroishi K, Tokunoh M, Saegusa T. Chelating properties of linear and branched poly(ethylenimine). Macrolecules. 1987; 20:1496-1500.
28. Kircheis R, Wightman L, Wagner E. Design and gene delivery activity of modified poly(ethylenimine). Adv. Drug Deliv. Rev. 2001; 53: 341-358.
29. Ogris M, Steinlein P, Kursa M, Mechtler K, Kircheis R, Wagner E. The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells. Gene Ther. 1998; 5:1425–33.
30. Oh YK, Suh D, Kim JM, Choi HG, Shin K, Ko JJ. Poly(ethylenimine)-mediated cellular uptake, nucleus trafficking and expression of cytokine plasmid DNA. Gene Ther. 2002; 9:1627–32.
31. Ferrari S, Moro E, Pettenazzo A, Behr JP, Zacchello F, Scarpa M. ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo. Gene Ther. 1997; 4:1100–6.
32. Wightman L, Kircheis R, Rossler V, Carotta S, Ruzicka R, Kursa M, Wagner E. Different behavior of branched and linear poly(ethylenimine) for gene delivery in vitro and in vivo. J. Gene Med. 2001; 3:362–72.
33. Gautam A, Densmore CL, Xu B, Waldrep JC. Enhanced gene expression in mouse lung after PEI–DNA aerosol delivery. Mol Ther. 2000; 2:63–70.
34. Shi L, Tang GP, Gao SJ, Ma YX, Liu BH, Li Y, et al. Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted poly(ethylenimine) led to prolonged transgene expression in the spinal cord. Gene Ther. 2003; 10:1179–88.
35. Gharwan H, Wightman L, Kircheis R, Wagner E, Zatloukal K. Nonviral gene transfer into fetal mouse livers (a comparison between the cationic polymer PEI and naked DNA). Gene Ther. 2003; 10:810–817.
36. Goula D, Remy JS, Erbacher P, Wasowicz M, Levi G, Abdallah B, et al. Size, diffusibility and transfection performance of linear PEI/DNA complexes in the mouse central nervous system. Gene Ther. 1998; 5:712–717.
37. Kwon OJ, Kang E, Choi JW, Kim SW, Yun CO. Therapeutic targeting of chitosan-PEG-folate–complexed oncolytic adenovirus for active and systemic cancer gene therapy. J. Control. Rel. 2013; 169(3): 257-65.
38. Nam JP, Nam K, Jung S, Nah JW, Kim SW. Evaluation of dendrimer type bio-reducible polymer as a siRNA delivery carrier for cancer therapy. J. Control. Rel. 2015; 209: 179-85.
39. Kim H, Nam K, Nam JP, Kim HS, Kim YM, Joo WS, Kim SW. VEGF therapeutic gene delivery using dendrimer type bio-reducible polymer into human mesenchymal stem cells (hMSCs). J Control. Rel. 2015; 220: 222-228.
40. Choi JW, Nam JP, Nam K, Lee YS, Yun CO, Kim SW. Oncolytic adenovirus coated with multi-degradable bio-reducible core-cross-linked poly(ethylenimine) for cancer gene therapy. Biomacromolecules. 2015; 16(7): 2132-43.
41. Lee YS, Choi JW, Oh JE, Yun CO, Kim SW. Human relaxin gene expression delivered by bio-reducible dendrimer polymer for post-infarct cardiac remodeling in rats. Biomaterials. 2016; 97: 164-75.
42. Yockman JW, Brumbach JH, Kim SW. Cleavable modifications to reducible poly(amido-ethylenimne)s to enhance nucleotide delivery. U.S. Patent Application Publication. No.: US2013/0149783 A1 (Jun.13, 2013), 1-8.
43. Kim HA, Nam K, Kim SW. Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing plasmid delivery. Biomaterials. 2014; 35(26): 7543-7552.