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Targeted Herceptin–dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI

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Abstract

A novel magnetic resonance imaging (MRI) contrast agent containing Herceptin is reported. The surfaces of superparamagnetic iron oxide nanoparticles were modified with dextran and conjugated with Herceptin (Herceptin–nanoparticles) to improve their dispersion, magnetization, and targeting of the specific receptors on cells. From analytical results, we found that Herceptin–nanoparticles were well dispersed in solutions of various pH range, and had no hysteresis, high saturation magnetization (80 emu/g), and low cytotoxicity to a variety of cells. Notably, the magnetic resonance enhancements for the different breast cancer cell lines (BT-474, SKBR-3, MDA-MB-231, and MCF-7) are proportional to the HER2/neu expression level in vitro. When Herceptin–nanoparticles were administered to mice bearing breast tumor allograft by intravenous injection, the tumor site was detected in T 2-weighted magnetic resonance images as a 45% enhancement drop, indicating a high level of accumulation of the contrast agent within the tumor sites. Therefore, targeting of cancer cells was observed by in vitro and in vivo MRI studies using Herceptin–nanoparticles contrast agent. In addition, Herceptin–nanoparticles enhancing the magnetic resonance signal intensity were sufficient to detect the cell lines with a low level of HER2/neu expression.

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References

  1. Sun C, Veiseh O, Gunn J, Fang C, Hansen S, Lee D, Sze R, Ellenbogen RG, Olson J, Zhang M (2008) Small 4:240–249

    Article  CAS  Google Scholar 

  2. Schellenberger E, Schnorr J, Reutelingsperger C, Ungethüm L, Meyer W, Taupitz M, Hamm B (2008) Small 4:225–230

    Article  PubMed  CAS  Google Scholar 

  3. Li Z, Tan B, Allix M, Cooper AI, Rosseinsky MJ (2008) Small 4:231–239

    Article  PubMed  CAS  Google Scholar 

  4. Kalambur VS, Longmire EK, Bischof JC (2007) Langmuir 23:12329–12336

    Article  PubMed  CAS  Google Scholar 

  5. Gupta AK, Gupta M (2005) Biomaterials 26:3995–4021

    Article  PubMed  CAS  Google Scholar 

  6. Yigit MV, Mazumdar D, Kim H-K, Lee JH, Odintsov B, Lu Y (2007) Chembiochem 8:1675–1678

    Article  PubMed  CAS  Google Scholar 

  7. Paul KG, Frigo TB, Groman JY, Groman EV (2004) Bioconjug Chem 15:194–401

    Article  CAS  Google Scholar 

  8. Koch AM, Reynolds F, Kircher MF, Merkle HP, Weissleder R, Josephson L (2003) Bioconjug Chem 14:1115–1121

    Article  PubMed  CAS  Google Scholar 

  9. Josephson L, Kircher MF, Mahmood U, Tang Y, Weissleder R (2002) Bioconjug Chem 13:554–560

    Article  PubMed  CAS  Google Scholar 

  10. Högemann D, Josephson L, Weissleder R, Basilion JP (2000) Bioconjug Chem 11:941–946

    Article  PubMed  CAS  Google Scholar 

  11. Lee H, Yu MK, Park S, Moon S, Min JJ, Jeong YY, Kang H-W, Jon S (2007) J. Am Chem Soc 129:12739–12745

    Article  CAS  Google Scholar 

  12. Choi H, Choi SR, Zhou R, Kung HF, Chen IW (2004) Acad Radiol 11:996–1004

    Article  PubMed  Google Scholar 

  13. Tran T, Engfeldt T, Orlova A, Sandström M, Feldwisch J, Abrahmsén L, Wennborg A, Tolmachev V, Karlström AE (2007) Bioconjug Chem 18:1956–1964

    Article  PubMed  CAS  Google Scholar 

  14. Germershaus O, Merdan T, Bakowsky U, Behe M, Kissel T (2006) Bioconjug Chem 17:1190–1199

    Article  PubMed  CAS  Google Scholar 

  15. Shukla R, Thomas TP, Peters JL, Desai AM, Kukowska-Latallo J, Patri AK, Kotlyar A, Baker JR (2006) Bioconjug Chem 17:1109–1115

    Article  PubMed  CAS  Google Scholar 

  16. Hilger I, Leistner Y, Berndt A, Fritsche C, Haas KM, Kosmehl H, Kaiser WA (2004) Eur Radiol 14:1124–1129

    Article  PubMed  Google Scholar 

  17. Pan M-H, Lin C-C, Lin J-K, Chen W-J (2007) J Agric Food Chem 55:5030–5037

    Article  PubMed  CAS  Google Scholar 

  18. Suna B, Ranganathana B, Feng S-S (2008) Biomaterials 29:475–486

    Article  CAS  Google Scholar 

  19. Bergman I, Whitaker-Dowling P, Gao Y, Griffin JA, Watkinse SC (2003) Virology 316:337–347

    Article  PubMed  CAS  Google Scholar 

  20. Colbern GT, Hiller AJ, Musterer RS, Working PK, Henderson IC (1999) J Inorg Biochem 77:117–120

    Article  PubMed  CAS  Google Scholar 

  21. Meares CF, Chmura AJ, Orton MS, Corneillie TM, Awhetstone P (2003) J Mol Recognit 16:255–259

    Article  PubMed  CAS  Google Scholar 

  22. Garmestania K, Milenica DE, Plascjakb PS, Brechbiel MW (2002) Nucl Med Biol 29:599–606

    Article  Google Scholar 

  23. Chen T-J, Cheng T-H, Hung Y-C, Lin K-T, Liuc G-C, Wang Y-M (2008) J Biomed Mater Res A 87:165–175

    PubMed  Google Scholar 

  24. Taktak S, Sosnovik D, Cima MJ, Weissleder R, Josephson L (2007) Anal Chem 79:8863–8869

    Article  PubMed  CAS  Google Scholar 

  25. Casula MF, Y-w Jun, Zaziski DJ, Chan EM, Corrias A, Alivisatos AP (2006) J Am Chem Soc 128:1675–1682

    Article  PubMed  CAS  Google Scholar 

  26. Park J, Lee E, Hwang N-M, Kang M, Kim SC, Hwang Y, Park J-G, Noh H-J, Kim J-Y, Park J-H, Hyeon T (2005) Angew Chem Int Ed 44:2872–2877

    Article  CAS  Google Scholar 

  27. Sun S, Zeng H (2002) J Am Chem Soc 124:8204–8205

    Article  PubMed  CAS  Google Scholar 

  28. Weissleder R, Elizondo G, Wittenberg J, Rabito CA, Bengele HH, Josephson L (1990) Radiology 175:485–493

    Google Scholar 

  29. Lee H, Lee E, Kim DK, Jang NK, Jeong YY, Jon S (2006) J Am Chem Soc 128:7383–7389

    Article  PubMed  CAS  Google Scholar 

  30. Cheng F-Y, Su C-H, Yang Y-S, Yeh C-S, Tsai C-Y, Wu C-L, Wu M-T, Shieh D-B (2005) Biomaterials 26:729–738

    Article  PubMed  CAS  Google Scholar 

  31. Shieh D-B, Cheng F-Y, Su C-H, Yeh C-S, Wu M-T, Wu Y-N, Tsai C-Y, Wu C-L, Chen D-H, Chou C-H (2005) Biomaterials 26:7183–7191

    Article  PubMed  CAS  Google Scholar 

  32. Varanda LC, Jafelicci M, Tartaj P, O’Grady K, González-Carreño T, Morales MP, Muñoz T, Serna CJ (2002) J Appl Phys 92:2079–2085

    Article  CAS  Google Scholar 

  33. Jun Y-W, Huh Y-M, Choi J-S, Lee J-H, Song H-T, Kim S, Yoon S, Kim K-S, Shin J-S, Suh J-S, Cheon J (2005) J Am Chem Soc 127:5732–5733

    Article  PubMed  CAS  Google Scholar 

  34. Huh Y-M, Jun Y-W, Song H-T, Kim S, Choi J-S, Lee J-H, Yoon S, Kim K-S, Shin J-S, Suh J-S, Cheon J (2005) J Am Chem Soc 127:12387–12391

    Article  PubMed  CAS  Google Scholar 

  35. Horák D, Babič M, Jendelová P, Herynek V, Trchova M, Pientka Z, Pollert E, Hájek M, Syková E (2007) Bioconjug Chem 8:635–644

    Article  CAS  Google Scholar 

  36. Sturla SJ, Irwin JJ, Loeppky RN, Mulvihill MJ, Searcey M (2007) ACS Chem Biol 2:286–292

    Article  PubMed  CAS  Google Scholar 

  37. Lee J-H, Huh Y-M, Jun Y-W, Seo J-W, Jang J-T, Song H-T, Kim S, Cho E-J, Yoon H-G, Suh J-S, Cheon J (2006) Nat Med 13:95–99

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the National Science Council of the Republic of China for financial support under contracts no. NSC 96-2627-M-037-001 and NSC 97-2623-7-037-001-NU. This research was also supported in part by grants from National Health Research Institutes under contract no. NHRI-EX-95-9424EI.

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Authors and Affiliations

  1. Department of Biological Science and Technology, National Chiao Tung University, 75 Bo-Ai Street, Hsinchu, 300, Taiwan

    Ting-Jung Chen & Yun-Ming Wang

  2. Department of Biological Science and Technology, Chung Hwa University of Medical Technology, 89, Wunhua 1st Street, Rende, Tainan County, 717, Taiwan

    Tsan-Hwang Cheng

  3. Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan

    Chiao-Yun Chen & Gin-Chung Liu

  4. Department of Radiology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Chiao-Yun Chen & Gin-Chung Liu

  5. Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan

    Sodio C. N. Hsu & Yun-Ming Wang

  6. Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan

    Tian-Lu Cheng

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  1. Ting-Jung Chen
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Correspondence to Yun-Ming Wang.

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Chen, TJ., Cheng, TH., Chen, CY. et al. Targeted Herceptin–dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI. J Biol Inorg Chem 14, 253–260 (2009). https://doi.org/10.1007/s00775-008-0445-9

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  • DOI: https://doi.org/10.1007/s00775-008-0445-9

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