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Received July 15, 2022
Accepted September 15, 2022
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Low generational cystamine core PAMAM derivatives modified with nuclear localization signal derived from lactoferrin as a gene carrier
Department of Chemical Engineering, University of New Hampshire, Durham, New Hampshire 03824, United States, USA 1Center for Scientific Instrumentation, Korea Basic Science Institute, 169-148 Gwahak-ro, Yuseong-gu, Daejeon 34133, Korea 2Research Center for Materials Analysis, Korea Basic Science Institute, 169-148 Gwahak-ro, Yuseong-gu, Daejeon 34133, Korea
Korean Journal of Chemical Engineering, February 2023, 40(2), 379-389(11), 10.1007/s11814-022-1293-y
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Abstract
Polyamidoamine (PAMAM) dendrimer has received much attention as an alternative to polyethylenimine (PEI) for gene delivery due to the relatively low cytotoxicity. In general, low generational PAMAM dendrimers have better biocompatibility than high generational dendrimers but suffer reduced transfection efficiency. Transfection efficiency can be improved by the modification of the polymer with nuclear localization signal (NLS) peptides. In this study, we modified low generational cystamine core PAMAM dendrimers (cPAMAM, generation 0, 1 and 2) with a lactoferrin-derived nuclear localization signal (NLS) peptide and evaluated transfection efficiency and cytotoxicity as a function of the number of conjugated NLS peptides using NIH 3T3, MCF-7 and human dermal fibroblasts (HDFs). The transfection efficiency of NLS-modified cPAMAM G2 was the highest among the cPAMAM derivatives and similar or higher than PEI 25 kDa. The cytotoxicity of cPAMAM derivatives was generation-dependent and significantly lower than PEI 25 kDa. Our study indicates that cPAMAM G2 conjugated with NLS is a promising candidate for gene delivery applications.
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References
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Ramamoorth M, Narvekar A, J. Clin. Diagn., 9(1), GE01 (2015)
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Ayuso E, Mol. Ther. Methods Clin. Dev., 3, 15049 (2016)
Wu P, Chen H, Jin R, Weng T, Ho JK, You C, Zhang L, Wang X, Han C, J. Transl. Med., 16(1), 1 (2018)
Rinoldi C, Zargarian S, Nakielski SP, Li X, Liguori A, Petronella F, Presutti D, Wang Q, Costantini M, De Sio L, Small Method., 5(9), 2100402 (2021)
Zhu L, Mahato RI, Expert Opin. Drug Deliv., 7(10), 1209 (2010)
Cheng Y, Yumul RC, Pun SH, Angew. Chem.-Int. Edit., 55(39), 12013 (2016)
Lee YS, Kim SW, J. Control. Release, 190, 424 (2014)
Liu Y, Li J, Shao K, Huang R, Ye L, Lou J, Jiang C, Biomaterials, 31(19), 5246 (2010)
Kim TH, Ihm JE, Choi YJ, Nah JW, Cho CS, J. Control. Release, 93(3), 389 (2003)
Benns JM, Choi JS, Mahato RI, Park JS, Kim SW, Bioconjugate Chem., 11(5), 637 (2000)
Lächelt U, Wagner E, Chem. Rev., 115(19), 11043 (2015)
Lee J, Jung J, Kim YJ, Lee E, Choi JS, Int. J. Pharm., 459(1-2), 10 (2014)
Ma K, Hu MX, Qi Y, Zou JH, Qiu LY, Jin Y, Ying XY, Sun HY, Biomaterials, 30(30), 6109 (2009)
Bae YM, Choi H, Lee S, Kang SH, Kim YT, Nam K, Park JS, Lee M, Choi JS, Bioconjugate Chem., 18(6), 2029 (2007)
Choi JS, Ko KS, Park JS, Kim YH, Kim SW, Lee M, Int. J. Pharm., 320(1-2), 171 (2006)
Boulikas T, Crit. Rev. Eukaryot. Gene Expr., 3(3), 193 (1993)
Pourianazar NT, Mutlu P, Gunduz U, J. Nanoparticle Res., 16(4), 1 (2014)
Moghimi SM, Symonds P, Murray JC, Hunter AC, Debska G, Szewczyk A, Mol. Ther., 11(6), 990 (2005)
Li X, Hao S, Han A, Yang Y, Fang G, Liu J, Wang S, J. Mater. Chem. B, 7(25), 4008 (2019)
Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown NB, D’emanuele A, Int. J. Pharm., 252(1-2), 263 (2003)
Haensler J, Szoka Jr FC, Bioconjugate Chem., 4(5), 372 (1993)
Kumari S, Kondapi AK, Int. J. Biol. Macromol., 108, 401 (2018)
Penco S, Scarfi S, Giovine M, Damonte G, Millo E, Villaggio B, Passalacqua M, Pozzolini M, Garrè C, Benatti U, Biotechnol. Appl. Biochem., 34(3), 151 (2001)
Lee J, Lee S, Kwon YE, Kim YJ, Choi JS, Macromole. Res., 27(4), 360 (2019)
Thuy LT, Mallick S, Choi JS, Int. J. Pharm., 492(1-2), 233 (2015)
Wade AM, Tucker HN, J. Nutr. Biochem., 9(6), 315 (1998)
Mecke A, Uppuluri S, Sassanella TM, Lee DK, Ramamoorthy A, Baker Jr JR, Bradford GO, Holl MMB, Chem. Phys. Lipids, 132(1), 3 (2004)
Geall AJ, Blagbrough IS, J. Pharm. Biomed., 22(5), 849 (2000)
Eliyahu H, Barenholz Y, Domb A, Molecules, 10(1), 34 (2005)
Monnery BD, Biomacromolcules, 22(10), 4060 (2021)
Bus T, Traeger A, Schubert US, J. Mater. Chem. B, 6(43), 6904 (2018)
Brunner S, Sauer T, Carotta S, Cotten M, Saltik M, Wagner E, Gene Ther., 7(5), 401 (2000)
Pantos A, Tsogas I, Paleos CM, Biochim. Biophys. Acta-Biomembr., 1778(4), 811 (2008)
Sakai N, Takeuchi T, Futaki S, Matile S, Chembiochem, 6(1), 114 (2005)
Chang H, Zhang J, Wang H, Lv J, Cheng Y, Biomacromolecules, 18(8), 2371 (2017)
Wang F, Hu K, Cheng Y, Acta Biomater., 29, 94 (2016)
Tsogas I, Tsiourvas D, Nounesis G, Paleos CM, Langmuir, 22(26), 11322 (2006)
Choi JS, Nam K, Park JY, Kim JB, Lee JK, Park JS, J. Control. Release, 99(3), 445 (2004)
Panté N, Kann M, J. Mol. Cell Biol., 13(2), 425 (2002)
Naha PC, Davoren M, Lyng FM, Byrne H, Toxicol. Appl. Pharmacol., 246(1-2), 91 (2010)
