Synthesis and Characterization of Magnetic Nanoparticle-Embedded Multi-Functional Polymeric Micelles for MRI-Guided Gene Delivery

Sang Joon Lee; Muthunarayanan Muthiah; Hyun Jin Lee; Hwa-Jeong Lee; Myeong-Ju Moon; Hui-Lian Che; Seon U. Heo; Hyun-Chul Lee; Yong Yeon Jeong; In-Kyu Park

Macromolecular Research, Vol.20, No.2, 188-196, February, 2012

DOI10.1007/s13233-012-0023-4 Export Citation

Synthesis and Characterization of Magnetic Nanoparticle-Embedded Multi-Functional Polymeric Micelles for MRI-Guided Gene Delivery

Sang Joon Lee^{1, 2}, Muthunarayanan Muthiah^{1, 2}, Hyun Jin Lee³, Hwa-Jeong Lee^{1, 2}, Myeong-Ju Moon⁴, Hui-Lian Che¹, Seon U. Heo⁴, Hyun-Chul Lee⁵, Yong Yeon Jeong⁴, and In-Kyu Park^{1, 2, †}

¹Department of Biomedical Sciences, Chonnam National University Medical School, Research Institute of Medical Science, Chonnam National University, Gwangju, 501-746, Korea
²Clinical Vaccine R&D Center, Chonnam National University, Gwangju, 501-746, Korea
³Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea
⁴Department of Radiology, Chonnam National University Medical School, Gwangju, 501-746, Korea
⁵Department of Microbiology, Chonnam National University Medical School, Gwangju, 501-746, Korea

E-mail:

Superparamagnetic iron oxide nanoparticle (SPION)-based diagnostic properties with accompanying therapeutics such as drugs or genes have been explored for improvement of their therapeutic efficacy. Positively charged SPION-loaded polymersomes was prepared to deliver genes to the target sites; this process was concomitantly monitored by magnetic resonance imaging (MRI). The surface characteristics and morphology were respectively measured by dynamic light scattering and transmission electron microscopy. The complex between the polymer and the pDNA was confirmed by a gel retardation assay. The transfection efficiency and cytotoxicity in vitro were tested by treating of the CT-26 colon cancer cell line with luciferase-expressing plasmids/SPION complex. MRI was also used to check the detectability of SPION in vitro and in vivo. A SPION-loaded polymersome carrying genetic materials was delivered and then accumulated in the tumor site of the murine colon cancer xenograft model after intravenous injection, possibly through a passive targeting mechanism. The accumulation was monitored using clinical MRI. This result indicates that the SPION-loaded polymersome can be applied to MR imageguided gene therapy.

Keywords:magnetic nanoparticles;polymeric micelles;magnetic resonance imaging (MRI);gene delivery.

[References]

Licciardi M, Campisi M, Cavallaro G, Carlisi B, Giammona G, Eur. Polym. J., 42, 823 (2006)
Chen S, Cheng SX, Zhuo RX, Macromol. Biosci., 11, 576 (2011)
Christian DA, Cai S, Bowen DM, Kim Y, Pajerowski JD, Discher DE, Eur. J. Pharm. Biopharm., 71, 463 (2009)
Levine DH, Ghoroghchian PP, Freudenberg J, Zhang G, Therien MJ, Greene MI, Hammer DA, Murali R, Methods., 46, 25 (2008)
Civiale C, Licciardi M, Cavallaro G, Giammona G, Mazzone G, Int. J. Pharm., 378, 177 (2009)
Kang H, Kim JD, Han SH, Chang IS, J. Control.Release., 81, 135 (2002)
Caliceti P, Quarta SM, Veronese FM, Cavallaro G, Pedone E, Giammona G, Biochim. Biophys. Acta., 1528, 177 (2001)
Sun SH, Zeng H, Robinson DB, Raoux S, Rice PM, Wang SX, Li GX, J. Am. Chem. Soc., 126(1), 273 (2004)
Lee HJ, Yang SR, An EJ, Kim JD, Macromolecules, 39(15), 4938 (2006)
Lee HJ, Jang KS, Jang S, Kim JW, Yang HM, Jeong YY, Kim JD, Chem. Commun., 46, 3559 (2010)
Lee Y, Chang JB, Kim HK, Park TG, Macromol. Res., 14(3), 359 (2006)
Giammona G, Civiale C, Licciardi M, Cavallaro G, Mazzone MG, Int. J. Pharm., 378, 177 (2009)
Hwang SJ, Jeong SY, Kim HJ, Kwak BK, Lee HY, Seong H, Shin BC, Yuk SH, Cho SH, Nanoscale Res. Lett., 5, 1970 (2010)
Matsumura Y, Maeda H, Cancer Res., 46, 6387 (1986)
Tanaka T, Shiramoto S, Miyashita M, Fujishima Y, Kaneo Y, Int. J. Pharm., 277, 39 (2004)
Lee SJ, Lee HJ, Moon MJ, Vu-Quang H, Lee HJ, Muthiah M, Che HL, Heo SU, Jeong HJ, Jeong YY, Park IK, J. Nanosci. Nanotechnol., Accepted 2011
Larsen EKU, Nielsen T, Wittenborn T, Birkedal H, Vorup-Jensen T, Jakobsen MH, Ostergaard L, Horsman MR, Besenbacher F, Howard KA, Kjems J, ACS Nano., 3, 1947 (2009)
Vasey PA, Kaye SB, Morrison R, Twelves C, Wilson P, Duncan R, Thomson AH, Murray LS, Hilditch TE, Murray T, Burtles S, Fraier D, Frigerio E, Cassidy J, Clin.Cancer Res., 5, 83 (1999)

[Referenced By]

[1] Licciardi M, Campisi M, Cavallaro G, Carlisi B, Giammona G, Eur. Polym. J., 42, 823 (2006)

[2] Chen S, Cheng SX, Zhuo RX, Macromol. Biosci., 11, 576 (2011)

[3] Christian DA, Cai S, Bowen DM, Kim Y, Pajerowski JD, Discher DE, Eur. J. Pharm. Biopharm., 71, 463 (2009)

[4] Levine DH, Ghoroghchian PP, Freudenberg J, Zhang G, Therien MJ, Greene MI, Hammer DA, Murali R, Methods., 46, 25 (2008)

[5] Civiale C, Licciardi M, Cavallaro G, Giammona G, Mazzone G, Int. J. Pharm., 378, 177 (2009)

[6] Kang H, Kim JD, Han SH, Chang IS, J. Control.Release., 81, 135 (2002)

[7] Caliceti P, Quarta SM, Veronese FM, Cavallaro G, Pedone E, Giammona G, Biochim. Biophys. Acta., 1528, 177 (2001)

[8] Sun SH, Zeng H, Robinson DB, Raoux S, Rice PM, Wang SX, Li GX, J. Am. Chem. Soc., 126(1), 273 (2004)

[9] Lee HJ, Yang SR, An EJ, Kim JD, Macromolecules, 39(15), 4938 (2006)

[10] Lee HJ, Jang KS, Jang S, Kim JW, Yang HM, Jeong YY, Kim JD, Chem. Commun., 46, 3559 (2010)

[11] Lee Y, Chang JB, Kim HK, Park TG, Macromol. Res., 14(3), 359 (2006)

[12] Giammona G, Civiale C, Licciardi M, Cavallaro G, Mazzone MG, Int. J. Pharm., 378, 177 (2009)

[13] Hwang SJ, Jeong SY, Kim HJ, Kwak BK, Lee HY, Seong H, Shin BC, Yuk SH, Cho SH, Nanoscale Res. Lett., 5, 1970 (2010)

[14] Matsumura Y, Maeda H, Cancer Res., 46, 6387 (1986)

[15] Tanaka T, Shiramoto S, Miyashita M, Fujishima Y, Kaneo Y, Int. J. Pharm., 277, 39 (2004)

[16] Lee SJ, Lee HJ, Moon MJ, Vu-Quang H, Lee HJ, Muthiah M, Che HL, Heo SU, Jeong HJ, Jeong YY, Park IK, J. Nanosci. Nanotechnol., Accepted 2011

[17] Larsen EKU, Nielsen T, Wittenborn T, Birkedal H, Vorup-Jensen T, Jakobsen MH, Ostergaard L, Horsman MR, Besenbacher F, Howard KA, Kjems J, ACS Nano., 3, 1947 (2009)

[18] Vasey PA, Kaye SB, Morrison R, Twelves C, Wilson P, Duncan R, Thomson AH, Murray LS, Hilditch TE, Murray T, Burtles S, Fraier D, Frigerio E, Cassidy J, Clin.Cancer Res., 5, 83 (1999)