Guanidinium-Incorporated Micelleplexes for Low Toxic and Efficient siRNA Delivery

Quan Truong Hoang; Tae-Young Heo; Dae Gun Choi; Soo-Hyung Choi; Min Suk Shim

Macromolecular Research, Vol.28, No.12, 1160-1165, November, 2020

DOI10.1007/s13233-020-8152-7 Export Citation

Guanidinium-Incorporated Micelleplexes for Low Toxic and Efficient siRNA Delivery

Quan Truong Hoang, Tae-Young Heo¹, Dae Gun Choi, Soo-Hyung Choi¹, and Min Suk Shim^†

Division of Bioengineering, Incheon National University, Incheon 22012, Korea
¹Department of Chemical Engineering, Hongik University, Seoul 04066, Korea

E-mail:

Small interfering RNA (siRNA)-based therapy has emerged as a powerful therapeutic tool due to its target-specific gene silencing. However, the therapeutic efficacy has been limited by poor cellular uptake, and therefore delivery vehicles are required to improve the cellular uptake. Herein, guanidinium-incorporated polyether-based block copolyelectrolytes were developed for improved cellular uptake and consequently increased gene silencing efficiency. Guanidinium-functionalized poly(ethylene oxide-b-allyl glycidyl ether) (G-PEO-PAGE) were prepared by living anionic ring opening polymerization of allyl glycidyl ether and post-modification to introduce guanidinium groups. G-PEO-PAGE provides efficient complexation with siRNA due to highly cationic charges of the guanidinium groups at physiological pH, resulting in significantly improved cellular uptake of siRNA and consequently increased gene silencing efficiency. In addition, G-PEO-PAGE showed significantly lower cytotoxicity compared to branched polyethylenimine as a commercial counterpart. This study demonstrates that guanidinium-incorporated block copolyelectrolytes have a great potential for efficient and low toxic siRNA delivery.

Keywords:Guanidinium;block copolyelectrolytes;siRNA;RNA interference;micelleplex;nanoparticle

[References]

Chalbatani GM, Dana H, Gharagozlou E, Mahmoodzadeh H, Zeinalinia E, Rezaeian O, Pilvar P, Ardaneh M, Meghdadi S, Memari F, Rad N, J. Biol. Sci., 17, 247 (2017)
Kim DH, Rossi JJ, Nat. Rev. Genet., 8, 173 (2007)
Filipowicz W, Jaskiewicz L, Kolb FA, Pillai RS, Curr. Opin. Struct. Biol., 15, 331 (2005)
He L, Hannon GJ, Nat. Rev. Genet., 5, 522 (2004)
Castanotto D, Rossi JJ, Nature, 457, 426 (2009)
Tatiparti K, Sau S, Kashaw S, Iyer A, Nanomaterials, 7, 77 (2017)
Kanasty R, Dorkin JR, Vegas A, Anderson D, Nat. Mater., 12(11), 967 (2013)
Biswas S, Deshpande PP, Navarro G, Dodwadkar NS, Torchilin VP, Biomaterials, 34, 1289 (2013)
Whitehead KA, Langer R, Anderson DG, Nat. Rev. Drug Discov., 8, 129 (2009)
Rettig GR, Behlke MA, Mol. Ther., 20, 483 (2012)
Zhang S, Zhao B, Jiang H, Wang B, Ma B, J. Control. Release, 123, 1 (2007)
Bhang SH, Kim KW, Rhee WJ, Shim MS, Macromol. Res., 26(12), 1135 (2018)
Tseng YC, Mozumdar S, Huang L, Adv. Drug Deliv. Rev., 61, 721 (2009)
Simeoni F, Morris MC, Heitz F, Divita G, Nucleic Acids Res., 31, 2717 (2003)
Cavallaro G, Sardo C, Craparo EF, Porsio B, Giammona G, Int. J. Pharm., 525, 313 (2017)
Navya PN, Kaphle A, Srinivas SP, Bhargava SK, Rotello VM, Daima HK, Nano Convergence, 6, 23 (2019)
Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z, J. Control. Release, 152, 2 (2011)
Farra R, Musiani F, Perrone F, Cemazar M, Kamensek U, Tonon F, et al.,, Molecules, 23, 777 (2018)
Nam K, Park JW, Bark H, Han J, Nah JW, Jang MK, Kim SW, Macromol. Res., 22(4), 370 (2014)
Pallan PS, Ganesh KN, Biochem. Biophys. Res. Commun., 222, 416 (1996)
Theodossiou TA, Pantos A, Tsogas I, Paleos CM, Chem. Med. Chem., 3, 1635 (2008)
Pantos A, Tsogas I, Paleos CM, Biochim. Biophys. Acta, 1778, 811 (2008)
deRonde BM, Torres JA, Minter LM, Tew GN, Biomacromolecules, 16(10), 3172 (2015)
Harada A, Kataoka K, J. Am. Chem. Soc., 121(39), 9241 (1999)
Kakizawa Y, Kataoka K, Langmuir, 18, 453 (2002)
Lindhoud S, de Vries R, Norde W, Cohen Stuart MA, Biomacromolecules, 8(7), 2219 (2007)
Heo TY, Kim I, Chen L, Lee E, Lee S, Choi SH, Polymers, 11, 455 (2019)
Lim P, Shin H, Moon B, Choi SH, Polym. Bull., 73(9), 2417 (2016)
Bernatowicz MS, Wu Y, Matsueda GR, J. Org. Chem., 57, 2497 (1992)
Hunt JN, Feldman KE, Lynd NA, Deek J, Campos LM, Spruell JM, Hernandez BM, Kramer EJ, Hawker CJ, Adv. Mater., 23(20), 2327 (2011)
Rejman J, Oberle V, Zuhorn IS, Hoekstra D, Biochem. J., 377, 159 (2004)
Shim MS, Wang X, Ragan R, Kwon YJ, Microsc. Res. Tech., 73, 845 (2010)
Kim C, Lee Y, Lee SH, Kim JS, Jeong JH, Park TG, Macromol. Res., 19(2), 166 (2011)
Dominska M, Dykxhoorn DM, J. Cell Sci., 123, 1183 (2010)
Malcolm DW, Varghese JJ, Sorrells JE, Ovitt CE, Benoit DSW, ACS Nano, 12, 187 (2018)
Frohlich E, Int. J. Nanomedicine, 7, 5577 (2012)
Wang J, Lu Z, Wientjes MG, Au JLS, AAPS J., 12, 492 (2010)

[Referenced By]

[1] Chalbatani GM, Dana H, Gharagozlou E, Mahmoodzadeh H, Zeinalinia E, Rezaeian O, Pilvar P, Ardaneh M, Meghdadi S, Memari F, Rad N, J. Biol. Sci., 17, 247 (2017)

[2] Kim DH, Rossi JJ, Nat. Rev. Genet., 8, 173 (2007)

[3] Filipowicz W, Jaskiewicz L, Kolb FA, Pillai RS, Curr. Opin. Struct. Biol., 15, 331 (2005)

[4] He L, Hannon GJ, Nat. Rev. Genet., 5, 522 (2004)

[5] Castanotto D, Rossi JJ, Nature, 457, 426 (2009)

[6] Tatiparti K, Sau S, Kashaw S, Iyer A, Nanomaterials, 7, 77 (2017)

[7] Kanasty R, Dorkin JR, Vegas A, Anderson D, Nat. Mater., 12(11), 967 (2013)

[8] Biswas S, Deshpande PP, Navarro G, Dodwadkar NS, Torchilin VP, Biomaterials, 34, 1289 (2013)

[9] Whitehead KA, Langer R, Anderson DG, Nat. Rev. Drug Discov., 8, 129 (2009)

[10] Rettig GR, Behlke MA, Mol. Ther., 20, 483 (2012)

[11] Zhang S, Zhao B, Jiang H, Wang B, Ma B, J. Control. Release, 123, 1 (2007)

[12] Bhang SH, Kim KW, Rhee WJ, Shim MS, Macromol. Res., 26(12), 1135 (2018)

[13] Tseng YC, Mozumdar S, Huang L, Adv. Drug Deliv. Rev., 61, 721 (2009)

[14] Simeoni F, Morris MC, Heitz F, Divita G, Nucleic Acids Res., 31, 2717 (2003)

[15] Cavallaro G, Sardo C, Craparo EF, Porsio B, Giammona G, Int. J. Pharm., 525, 313 (2017)

[16] Navya PN, Kaphle A, Srinivas SP, Bhargava SK, Rotello VM, Daima HK, Nano Convergence, 6, 23 (2019)

[17] Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z, J. Control. Release, 152, 2 (2011)

[18] Farra R, Musiani F, Perrone F, Cemazar M, Kamensek U, Tonon F, et al.,, Molecules, 23, 777 (2018)

[19] Nam K, Park JW, Bark H, Han J, Nah JW, Jang MK, Kim SW, Macromol. Res., 22(4), 370 (2014)

[20] Pallan PS, Ganesh KN, Biochem. Biophys. Res. Commun., 222, 416 (1996)

[21] Theodossiou TA, Pantos A, Tsogas I, Paleos CM, Chem. Med. Chem., 3, 1635 (2008)

[22] Pantos A, Tsogas I, Paleos CM, Biochim. Biophys. Acta, 1778, 811 (2008)

[23] deRonde BM, Torres JA, Minter LM, Tew GN, Biomacromolecules, 16(10), 3172 (2015)

[24] Harada A, Kataoka K, J. Am. Chem. Soc., 121(39), 9241 (1999)

[25] Kakizawa Y, Kataoka K, Langmuir, 18, 453 (2002)

[26] Lindhoud S, de Vries R, Norde W, Cohen Stuart MA, Biomacromolecules, 8(7), 2219 (2007)

[27] Heo TY, Kim I, Chen L, Lee E, Lee S, Choi SH, Polymers, 11, 455 (2019)

[28] Lim P, Shin H, Moon B, Choi SH, Polym. Bull., 73(9), 2417 (2016)

[29] Bernatowicz MS, Wu Y, Matsueda GR, J. Org. Chem., 57, 2497 (1992)

[30] Hunt JN, Feldman KE, Lynd NA, Deek J, Campos LM, Spruell JM, Hernandez BM, Kramer EJ, Hawker CJ, Adv. Mater., 23(20), 2327 (2011)

[31] Rejman J, Oberle V, Zuhorn IS, Hoekstra D, Biochem. J., 377, 159 (2004)

[32] Shim MS, Wang X, Ragan R, Kwon YJ, Microsc. Res. Tech., 73, 845 (2010)

[33] Kim C, Lee Y, Lee SH, Kim JS, Jeong JH, Park TG, Macromol. Res., 19(2), 166 (2011)

[34] Dominska M, Dykxhoorn DM, J. Cell Sci., 123, 1183 (2010)

[35] Malcolm DW, Varghese JJ, Sorrells JE, Ovitt CE, Benoit DSW, ACS Nano, 12, 187 (2018)

[36] Frohlich E, Int. J. Nanomedicine, 7, 5577 (2012)

[37] Wang J, Lu Z, Wientjes MG, Au JLS, AAPS J., 12, 492 (2010)