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Received May 19, 2022
Accepted September 15, 2022
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Synthesis and characterization of oligo aminoglycosides and polyethylenimine conjugates as polymeric gene carriers
Department of Biochemistry, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea 1Department of Mechanical Engineering, University of Delaware, Newark, Delaware, United States, 19716, USA
joonsig@cnu.ac.kr
Korean Journal of Chemical Engineering, February 2023, 40(2), 325-336(12), 10.1007/s11814-022-1296-8
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Abstract
In this study, a new kind of antibiotic drug-polymer conjugate, the kanamycin-methyl acrylate-polyethylenimine (KMP) polymer, was synthesized and characterized as gene carrier. Previous reports have shown that the modification of low molecular weight polyethylenimine (LMW-PEI) improves the transfection efficiency and decreases the toxicity. Kanamycin can be hydrolyzed under an acidic environment owing to the glycosidic bond. In this physicochemical study, the properties of the kanamycin-based hybrid polymers conjugated with various LMW-PEIs, such as 0.6, 1.2, and 2 kDa polyethylenimine (PEI), were investigated by 1H NMR, FT-IR, and their buffering capacity was assayed by acid-base titration method. Gel electrophoresis and picogreen assay were performed to evaluate the ability to bind with plasmid DNA. The polyplexes were nanosized with a net positive charge. The cytotoxicity and transfection efficiency were evaluated using human cervical carcinoma (HeLa) cells. KMPs exhibited lower toxicity than PEI 25 kDa, and higher transfection efficiency compared to the native LMW-PEIs.
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References
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Wang YQ, Asakawa A, Inui A, Kosai K, Expert Opin. Biol. Ther., 10, 1405 (2010)
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Sudhakar V, Richardson RM, Neurotherapeutics, 16, 166 (2019)
Miller R, Hinderer C, Dyer C, Johansson J, Bell P, Wilson JM, Hum. Gene Ther., 30, A91 (2019)
Dastjerd NT, Valibeik A, Monfared SR, Goodarzi G, Sarabi MM, Hajabdollahi F, Maniati M, Amri J, Tehrani SS, J. Cell. Biochem., 40, 28 (2022)
Ramamoorth M, Narvekar A, J. Clin. Diagnostic Res., 9, GE01 (2015)
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Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG, Nat. Rev. Genet., 15, 541 (2014)
Huh MS, Lee EJ, Koo H, Yhee JY, Oh KS, Son S, Lee S, Kim SH, Kwon IC, Kim K, Top. Curr. Chem., 375(2), 31 (2017)
Salatin S, Jelvehgari M, Iran. J. Pharm. Sci., 23, 84 (2017)
Barua S, Ramos J, Potta T, Taylor D, Huang HC, Montanez G, Rege K, Comb. Chem. High Throughput Screen., 14, 908 (2011)
Teagle AR, Birchall JC, Hargest R, Skin Pharmacol. Physiol., 29, 119 (2016)
Chen JL, Wang H, Gao JQ, Chen HL, Liang WQ, Int. J. Pharm., 343, 255 (2007)
Dass CR, Choong PFM, J. Control. Release, 113, 155 (2006)
Zakeri A, Kouhbanani MAJ, Beheshtkhoo N, Beigi V, Mousavi SM, Hashemi SAR, Zade AK, Amani AM, J. Exp. Nanosci., 9(1), 1488497 (2018)
Benjaminsen RV, Mattebjerg MA, Henriksen JR, Moghimi SM, Andresen TL, Mol. Ther., 21, 149 (2013)
Degors IMS, Wang C, Rehman ZU, Zuhorn IS, Acc. Chem. Res., 52, 1750 (2019)
Chen CK, Huang PK, Law WC, Chu CH, Chen NT, Lo LW, Int. J. Nanomed., 15, 2131 (2020)
Liu Q, Su RC, Yi WJ, Zhao ZG, Molecules, 4, 22 (2017)
Gosselin MA, Guo WJ, Lee RJ, Bioconjugate Chem., 12, 989 (2001)
Kim TH, Choi H, Yu GS, Lee J, Choi JS, Macromol. Res., 21, 1097 (2013)
Lee YH, Park HI, Choi JS, Carbohydr. Polym., 137, 669 (2016)
Krause KM, Serio AW, Kane TR, Connolly LE, Cold Spring Harb. Perspect. Med. CSH., 6(6), a027029 (2016)
Zhang Y, Zhou Z, Zhu X, Chen M, Eur. J. Pharm. Sci., 105, 33 (2017)
Sainlos M, Belmont P, Vigneron JP, Lehn P, Lehn JM, Eur. J. Org. Chem., 2003, 2764 (2003)
Chen MS, Wu JL, Zhou LZ, Jin CY, Tu CL, Zhu BS, Wu FA, Zhu Q, Zhu XY, Yan DY, Mater. Today Commun., 25, 101692 (2020)
Wang MX, Wu B, Shah SN, Lu PJ, Lu QL, Mol. Ther. Nucleic Acids., 16, 663 (2019)
Godeshala S, Nitiyanandan R, Thompson B, Goklany S, Nielsen DR, Rege K, Bioeng. Transl. Med., 1, 220 (2016)
Chen CK, Huang PK, Law WC, Chu CH, Chen NT, Lo LW, Int. J. Nanomed., 15, 2131 (2020)