Herceptin Conjugated PCL-PEG-PCL Triblock Copolymer for Cancer Targeting and Imaging

Junki Kim; Md. Nurunnabi; Yeon Jeong Oh; Sung Young Park; Yong-kyu Lee

Macromolecular Research, Vol.20, No.8, 875-882, August, 2012

DOI10.1007/s13233-012-0172-5 Export Citation

Herceptin Conjugated PCL-PEG-PCL Triblock Copolymer for Cancer Targeting and Imaging

Junki Kim, Md. Nurunnabi, Yeon Jeong Oh, Sung Young Park^†, and Yong-kyu Lee^†

Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungbuk, 380-702, Korea

E-mail:,

Herceptin conjugated biodegradable poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)(PCL-PEG-PCL, PCEC) triblock copolymer has shown potential applications in drug delivery systems. In order to synthesize PCEC triblock copolymer, oligo(t-BMA) grafted PEG in the backbone were first prepared by graft radical polymerization of t-BMA in the presence of t-butylperoxybenzoate as an initiator. Then, PCL was introduced into the backbone in the presense of an initiator and a catalyst. The final product, Herceptin conjugated PCEC triblock copolymer, was confirmed with the amide bond formation between the carboxylic group of grafted PCEC polymers and the amine group of Herceptin. The targeted triblock copolymer formed nano-sized micelles with spherical shapes. The average size was in the range of 100-150 nm in diameter, showing similar fluorescent intensities for 6 days. The results of the MTT assay demonstrated that the MDA-MB231 cancer cells are more sensitive for the Herceptin conjugated PCEC micelle due to the over-expression of HER-2 receptors. The guantum dots (QDs) loaded PCEC micelles were up-taken by the MDA-MB231 cell, through the HER-2 receptor, by active binding. The overall data demonstrated that the QDs loaded PCEC micelles could be used for active targeted delivery, cancer therapy, and non-invasive imaging.

Keywords:Herceptin;active targeting;PCEC triblock copolymer;micelles;imaging.

[References]

Nurunnabi M, Cho KJ, Choi JS, Huh KM, Lee YK, Biomaterials., 31, 5436 (2010)
Dios ASD, Diaz-Garcia ME, Anal. Chim. Acta., 666, 1 (2010)
Gorelikov I, Martin AL, Seo M, Matsuura N, Langmuir., DOI: 10.1021/la202679p.
Fei X, Gu Y, Wang J, Jia G, Liu Z, J. Lumin., 131, 291 (2011)
Jagadeeswari S, Jhonsi MA, Kathiravan A, Renganathan R, J. Lumin., 131, 597 (2011)
Cheng L, Yang K, Shao M, Lee ST, Liu Z, J. Phys.Chem. C., 115, 2686 (2011)
Yang P, Ando M, Murase N, J. Colloid Interface Sci., 361(1), 9 (2011)
Dai M, Xu X, Song J, Fu SZ, Gou ML, Luo F, Qian ZY, Cancer Lett., 312, 189 (2011)
Kim JS, Cho KJ, Tran TH, Nurunnabi M, Moon TH, Hong SM, Lee YK, J. Colloid Interface Sci., 353(2), 363 (2011)
Falini G, Sartor G, Fabbri D, Vergni P, Fermani S, Belcher AM, Stucky GD, Morse DE, J. Struct. Biol., 173(1), 128 (2011)
Newkome GR, Shreiner CD, Polymer, 49(1), 1 (2008)
Allen TM, Cullis PR, Science., 303, 1818 (2004)
Chakravarthi SS, Robinson DH, Int. J. Pharm., 409, 111 (2011)
Park J, Mattessich T, Jay SM, Agawu A, Saltzman WM, Fahmy TM, J. Control. Release., 156, 109 (2011)
Clift MJD, Brandenberger C, Rothen-Rutishauser B, Brown DM, Stone V, Toxicology., 286, 58 (2011)
Scott AD, Orsi A, Ward C, Bradford R, Food Chem.Toxicol., DOI:10.1016/j.fct.2011.01.022.
Leung MF, Zhu JM, Harris FW, Li P, Macromol. Rapid Commun., 25(21), 1819 (2004)
Patani N, Mokbel K, Surgical Oncology., 19, 11 (2010)
Arya G, Vandana M, Acharya S, Sahoo SK, Nanomedicine., 7, 859 (2011)
Torchilin V, Adv. Drug Deliv. Rev., 63, 131 (2011)
Acharya S, Sahoo SK, Adv. Drug Deliv. Rev., 63, 170 (2011)
Danhier F, Feron O, Preat V, J. Control. Release., 148, 135 (2010)
Beduneau A, Saulnier P, Benoit JP, Biomaterials., 28, 4947 (2007)

[1] Nurunnabi M, Cho KJ, Choi JS, Huh KM, Lee YK, Biomaterials., 31, 5436 (2010)

[2] Dios ASD, Diaz-Garcia ME, Anal. Chim. Acta., 666, 1 (2010)

[3] Gorelikov I, Martin AL, Seo M, Matsuura N, Langmuir., DOI: 10.1021/la202679p.

[4] Fei X, Gu Y, Wang J, Jia G, Liu Z, J. Lumin., 131, 291 (2011)

[5] Jagadeeswari S, Jhonsi MA, Kathiravan A, Renganathan R, J. Lumin., 131, 597 (2011)

[6] Cheng L, Yang K, Shao M, Lee ST, Liu Z, J. Phys.Chem. C., 115, 2686 (2011)

[7] Yang P, Ando M, Murase N, J. Colloid Interface Sci., 361(1), 9 (2011)

[8] Dai M, Xu X, Song J, Fu SZ, Gou ML, Luo F, Qian ZY, Cancer Lett., 312, 189 (2011)

[9] Kim JS, Cho KJ, Tran TH, Nurunnabi M, Moon TH, Hong SM, Lee YK, J. Colloid Interface Sci., 353(2), 363 (2011)

[10] Falini G, Sartor G, Fabbri D, Vergni P, Fermani S, Belcher AM, Stucky GD, Morse DE, J. Struct. Biol., 173(1), 128 (2011)

[11] Newkome GR, Shreiner CD, Polymer, 49(1), 1 (2008)

[12] Allen TM, Cullis PR, Science., 303, 1818 (2004)

[13] Chakravarthi SS, Robinson DH, Int. J. Pharm., 409, 111 (2011)

[14] Park J, Mattessich T, Jay SM, Agawu A, Saltzman WM, Fahmy TM, J. Control. Release., 156, 109 (2011)

[15] Clift MJD, Brandenberger C, Rothen-Rutishauser B, Brown DM, Stone V, Toxicology., 286, 58 (2011)

[16] Scott AD, Orsi A, Ward C, Bradford R, Food Chem.Toxicol., DOI:10.1016/j.fct.2011.01.022.

[17] Leung MF, Zhu JM, Harris FW, Li P, Macromol. Rapid Commun., 25(21), 1819 (2004)

[18] Patani N, Mokbel K, Surgical Oncology., 19, 11 (2010)

[19] Arya G, Vandana M, Acharya S, Sahoo SK, Nanomedicine., 7, 859 (2011)

[20] Torchilin V, Adv. Drug Deliv. Rev., 63, 131 (2011)

[21] Acharya S, Sahoo SK, Adv. Drug Deliv. Rev., 63, 170 (2011)

[22] Danhier F, Feron O, Preat V, J. Control. Release., 148, 135 (2010)

[23] Beduneau A, Saulnier P, Benoit JP, Biomaterials., 28, 4947 (2007)