Glutathione-responsive PEGylated GQD-based nanomaterials for diagnosis and treatment of breast cancer

Na Re Ko; Sung Hwa Hong; Md Nafiujjaman; Seong Yeong An; Vishnu Revuri; Sang Ju Lee; Il Keun Kwon; Yong-kyu Lee; Seung Jun Oh

Journal of Industrial and Engineering Chemistry, Vol.71, 301-307, March, 2019

DOI10.1016/j.jiec.2018.11.039 Export Citation

Glutathione-responsive PEGylated GQD-based nanomaterials for diagnosis and treatment of breast cancer

Na Re Ko^{1, 2}, Sung Hwa Hong³, Md Nafiujjaman⁴, Seong Yeong An⁵, Vishnu Revuri⁶, Sang Ju Lee², Il Keun Kwon⁷, Yong-kyu Lee^{6, †}, and Seung Jun Oh^{1, 2, †}

¹Department of Medicine, University of Ulsan College of Medicine,, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
²Department of Nuclear Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
³Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, M5S 3E5, Canada
⁴Department of Nanomedicine, The Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA
⁵Department of Dentistry, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
⁶Department of Green Bioengineering, Korea National University of Transportation, 50 Daehak-ro, Daesowon-myeon, Cheongju, Chungcheongbuk-do 27469, Republic of Korea
⁷Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea

E-mail:,

Graphene quantum dots-based nanoparticles (GQD-NPs) with reduction-responsive properties were synthesized via conjugation with two precursors, doxorubicin-disulfide-GQD that endowed the drug loading capability and polyethylene glycol-disulfide-Herceptin that enhanced the half-life and conferred active targeting ability towards HER2-overexpressed cancer. Disulfide linkages between the compartments are cleaved at a physiologically relevant concentration of glutathione in cancer cells, resulting a controlled release of drugs. In vitro analysis confirmed successful internalization of GQD-NPs in the cytoplasm and enhanced cellular uptake of DOX in HER2-positive breast cancer cells. The GQD-NPs show potential as a theranostic agent for HER2-overexpressed breast cancer cells.

Keywords:Quantum dots;PEGylation;Stimuli-responsive degradation;Glutathione;Bio-imaging

[References]

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F, Int. J. Cancer, 136, E359 (2015)
Torchilin VP, Nat. Rev. Drug Discov., 13, 813 (2014)
Tibbitt MW, Dahlman JE, Langer R, J. Am. Chem. Soc., 138(3), 704 (2016)
Pathak Y, Recent Developments in Nanoparticulate Drug Delivery Systems, CRC Press, pp.19 2016.
Lim SY, Shen W, Gao Z, Chem. Soc. Rev., 44, 362 (2015)
Zheng XT, Ananthanarayanan A, Luo KQ, Chen P, Small, 11, 1620 (2015)
Ding H, Zhang F, Zhao C, Lv Y, Ma G, Wei W, Tian Z, ACS Appl. Mater. Interfaces, 9, 27396 (2017)
Dong J, Wang K, Sun L, Sun B, Yang M, Chen H, Wang Y, Sun J, Dong L, Sens. Actuators B-Chem., 256, 616 (2018)
Thakur M, Kumawat MK, Srivastava R, R.S.C Adv., 7, 5251 (2017)
Bagalkot V, Zhang L, Levy-Nissenbaum E, Jon S, Kantoff PW, Langer R, Farokhzad OC, Nano Lett., 7, 3065 (2007)
Derfus AM, Chan WC, Bhatia SN, Nano Lett., 4, 11 (2004)
Ko NR, Nafiujjaman M, Lee JS, Lim HN, Lee YK, Kwon IK, RSC Adv., 7, 11420 (2017)
Zhang W, Cao Y, Tian P, Guo F, Tian Y, Zheng W, Ji X, Liu J, ACS Appl. Mater. Interfaces, 8, 32440 (2016)
Nurunnabi M, Parvez K, Nafiujjaman M, Revuri V, Khan HA, Feng X, Lee YK, RSC Adv., 5, 42141 (2015)
Hauck TS, Anderson RE, Fischer HC, Newbigging S, Chan WC, Small, 6, 138 (2010)
Ballou B, Lagerholm BC, Ernst LA, Bruchez MP, Waggoner AS, Bioconjug. Chem., 15, 79 (2004)
Maldiney T, Richard C, Seguin J, Wattier N, Bessodes M, Scherman D, ACS Nano, 5, 854 (2011)
Harris JM, Chess RB, Nat. Rev. Drug Discov., 2, 214 (2003)
Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, Bawendi MG, Frangioni JV, Nat. Biotechnol., 25, 1165 (2007)
Mura S, Nicolas J, Couvreur P, Nat. Mater., 12(11), 991 (2013)
Yang K, Feng L, Liu Z, Adv. Drug Deliv. Rev., 105, 228 (2016)
Hu H, Yu J, Li Y, Zhao J, Dong H, J. Biomed. Mater. Res. A, 100, 141 (2012)
Quinn JF, Whittaker MR, Davis TP, Polym. Chem., 8, 97 (2017)
Xu X, Saw PE, Tao W, Li Y, Ji X, Bhasin S, Liu Y, Ayyash D, Rasmussen J, Huo M, Adv. Mater., 29, 170014 (2017)
Zhang H, Fei JB, Yan XH, Wang AH, Li JB, Adv. Funct. Mater., 25(8), 1193 (2015)
Wang H, Miao WJ, Wang F, Cheng YY, Biomacromolecules, 19(6), 2194 (2018)
Akimoto J, Nakayama M, Okano T, J. Control. Release, 193, 2 (2014)
Estelrich J, Escribano E, Queralt J, Busquets MA, Int. J. Mol. Sci., 16(4), 8070 (2015)
Hassan SS, Rechnitz G, Anal. Chem., 54, 1972 (1982)
Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL, Biol. Chem., 390, 191 (2009)
Wen H, Dong C, Dong H, Shen A, Xia W, Cai X, Song Y, Li X, Li Y, Shi D, Small, 8, 760 (2012)
Li Y, Feng L, Shi X, Wang X, Yang Y, Yang K, Liu T, Yang G, Liu Z, Small, 10, 1544 (2014)
Chen H, Wang Z, Zong S, Wu L, Chen P, Zhu D, Wang C, Xu S, Cui Y, ACS Appl. Mater. Interfaces, 6, 17526 (2014)
Ko NR, Oh JK, Biomacromolecules, 15(8), 3180 (2014)

[Referenced By]

[1] Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F, Int. J. Cancer, 136, E359 (2015)

[2] Torchilin VP, Nat. Rev. Drug Discov., 13, 813 (2014)

[3] Tibbitt MW, Dahlman JE, Langer R, J. Am. Chem. Soc., 138(3), 704 (2016)

[4] Pathak Y, Recent Developments in Nanoparticulate Drug Delivery Systems, CRC Press, pp.19 2016.

[5] Lim SY, Shen W, Gao Z, Chem. Soc. Rev., 44, 362 (2015)

[6] Zheng XT, Ananthanarayanan A, Luo KQ, Chen P, Small, 11, 1620 (2015)

[7] Ding H, Zhang F, Zhao C, Lv Y, Ma G, Wei W, Tian Z, ACS Appl. Mater. Interfaces, 9, 27396 (2017)

[8] Dong J, Wang K, Sun L, Sun B, Yang M, Chen H, Wang Y, Sun J, Dong L, Sens. Actuators B-Chem., 256, 616 (2018)

[9] Thakur M, Kumawat MK, Srivastava R, R.S.C Adv., 7, 5251 (2017)

[10] Bagalkot V, Zhang L, Levy-Nissenbaum E, Jon S, Kantoff PW, Langer R, Farokhzad OC, Nano Lett., 7, 3065 (2007)

[11] Derfus AM, Chan WC, Bhatia SN, Nano Lett., 4, 11 (2004)

[12] Ko NR, Nafiujjaman M, Lee JS, Lim HN, Lee YK, Kwon IK, RSC Adv., 7, 11420 (2017)

[13] Zhang W, Cao Y, Tian P, Guo F, Tian Y, Zheng W, Ji X, Liu J, ACS Appl. Mater. Interfaces, 8, 32440 (2016)

[14] Nurunnabi M, Parvez K, Nafiujjaman M, Revuri V, Khan HA, Feng X, Lee YK, RSC Adv., 5, 42141 (2015)

[15] Hauck TS, Anderson RE, Fischer HC, Newbigging S, Chan WC, Small, 6, 138 (2010)

[16] Ballou B, Lagerholm BC, Ernst LA, Bruchez MP, Waggoner AS, Bioconjug. Chem., 15, 79 (2004)

[17] Maldiney T, Richard C, Seguin J, Wattier N, Bessodes M, Scherman D, ACS Nano, 5, 854 (2011)

[18] Harris JM, Chess RB, Nat. Rev. Drug Discov., 2, 214 (2003)

[19] Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, Bawendi MG, Frangioni JV, Nat. Biotechnol., 25, 1165 (2007)

[20] Mura S, Nicolas J, Couvreur P, Nat. Mater., 12(11), 991 (2013)

[21] Yang K, Feng L, Liu Z, Adv. Drug Deliv. Rev., 105, 228 (2016)

[22] Hu H, Yu J, Li Y, Zhao J, Dong H, J. Biomed. Mater. Res. A, 100, 141 (2012)

[23] Quinn JF, Whittaker MR, Davis TP, Polym. Chem., 8, 97 (2017)

[24] Xu X, Saw PE, Tao W, Li Y, Ji X, Bhasin S, Liu Y, Ayyash D, Rasmussen J, Huo M, Adv. Mater., 29, 170014 (2017)

[25] Zhang H, Fei JB, Yan XH, Wang AH, Li JB, Adv. Funct. Mater., 25(8), 1193 (2015)

[26] Wang H, Miao WJ, Wang F, Cheng YY, Biomacromolecules, 19(6), 2194 (2018)

[27] Akimoto J, Nakayama M, Okano T, J. Control. Release, 193, 2 (2014)

[28] Estelrich J, Escribano E, Queralt J, Busquets MA, Int. J. Mol. Sci., 16(4), 8070 (2015)

[29] Hassan SS, Rechnitz G, Anal. Chem., 54, 1972 (1982)

[30] Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL, Biol. Chem., 390, 191 (2009)

[31] Wen H, Dong C, Dong H, Shen A, Xia W, Cai X, Song Y, Li X, Li Y, Shi D, Small, 8, 760 (2012)

[32] Li Y, Feng L, Shi X, Wang X, Yang Y, Yang K, Liu T, Yang G, Liu Z, Small, 10, 1544 (2014)

[33] Chen H, Wang Z, Zong S, Wu L, Chen P, Zhu D, Wang C, Xu S, Cui Y, ACS Appl. Mater. Interfaces, 6, 17526 (2014)

[34] Ko NR, Oh JK, Biomacromolecules, 15(8), 3180 (2014)