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Amphiphilic dextran/magnetite nanocomposites as magnetic resonance imaging probes

  • Special Topic/Articles/Biomedical Materials
  • Published:
Chinese Science Bulletin

Abstract

Superparamagnetic iron oxide (SPIO) nanoparticles are effective contrast agents for enhancement of magnetic resonance imaging at the tissue, cellular or even molecular levels. High quality SPIO nanoparticles can be synthesized in the organic phase but need to be transferred into water before any biomedical applications. In this study, amphiphilic poly(ε-caprolactone) grafted dextran (Dex-g-PCL) was used as carriers for particle encapsulation and stabilization in the aqueous phase. Multiple SPIO nanoparticles were self-assembled together with the help of Dex-g-PCL during phase transfer from chloroform to water, and diameters of Dex-g-PCL/SPIO nanocomposites were (64 ± 22) nm through dynamic light scattering measurement. These nanocomposites were superparamagnetic at 300 K with saturated magnetization of 88 emu/g Fe. In the magnetic field of 1.5 T, Dex-g-PCL/SPIO nanocomposites had a T2 relaxivity of 363 Fe mL·mol−1·s−1. This unique nanocomposite brought significant mouse liver contrast with signal intensity changes of −60% at 5 min after intravenous administration. However, uptake of Dex-g-PCL/SPIO nanocomposites in liver reticuloendothelial cells (Kupffer cells) did not immediately happen at shorter time points (〈4 h) as verified by histology studies, and it was evident that more iron staining would be located in Kupffer cells 24 h after contrast agent administration. After 24 h and 10 d, the signal intensities (SI) gradually recovered, and SI changes were −44% and −31%, respectively. From our observation, the time window for enhanced-MRI could last at least 12 days and totally recovered after 16 days. This novel sensitive MRI contrast agent may find potential applications in discovering small liver lesions such as early tumor diagnosis.

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References

  1. Feng L, Song Y, Wan M, et al. Research progress of magnetic iron oxide nanoparticles. Chin Sci Bull, 2001, 46: 1321–1325

    Google Scholar 

  2. Yan G., Zhuo R. Research progress of magnetic resonance imaging contrast agents. Chin Sci Bull, 2001, 46: 1233–1237

    Article  Google Scholar 

  3. Bulte J W, Kraitchman D L. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed, 2004, 17: 484–499

    Article  Google Scholar 

  4. Weissleder R, Mahmood U. Molecular imaging. Radiology, 2001, 219: 316–333

    Google Scholar 

  5. Jana N R, Chen Y, Peng X. Size- and shape-controlled magnetic (Cr, Mn, Fe, Co, Ni) oxide nanocrystals via a simple and general approach. Chem Mater, 2004, 16: 3931–3935

    Article  Google Scholar 

  6. Park J, An K, Hwang Y, et al. Ultra-large-scale syntheses of monodisperse nanocrystals. Nat Mater, 2004, 3: 891–895

    Article  Google Scholar 

  7. Sun S H, Zeng H, Robinson D B, et al. Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. J Am Chem Soc, 2004, 126: 273–279

    Article  Google Scholar 

  8. Jun Y W, Huh Y M, Choi J S, et al. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J Am Chem Soc, 2005, 127: 5732–5733

    Article  Google Scholar 

  9. Song H T, Choi J S, Huh Y M, et al. Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling. J Am Chem Soc, 2005, 127: 9992–9993

    Article  Google Scholar 

  10. Kim S W, Kim S, Tracy J B, et al. Phosphine oxide polymer for water-soluble nanoparticles. J Am Chem Soc, 2005, 127: 4556–4557

    Article  Google Scholar 

  11. Kakizawa Y, Kataoka K. Block copolymer micelles for delivery of gene and related compounds. Adv Drug Deliv Rev, 2002, 54: 203–222

    Article  Google Scholar 

  12. Kwon G S, Okano T. Polymeric micelles as new drug carriers. Adv Drug Deliv Rev, 1996, 21: 107–116

    Article  Google Scholar 

  13. Croy S R, Kwon G S. Polymeric micelles for drug delivery. Curr Pharm Des, 2006, 12: 4669–4684

    Article  Google Scholar 

  14. Nasongkla N, Bey E, Ren J, et al. Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett, 2006, 6: 2427–2430

    Article  Google Scholar 

  15. Nasongkla N, Shuai X, Ai H, et al. cRGD-functionalized polymer micelles for targeted doxorubicin delivery. Angew Chem Int Ed Engl, 2004, 43: 6323–6327

    Article  Google Scholar 

  16. Shuai X, Ai H, Nasongkla N, et al. Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. J Control Release, 2004, 98: 415–426

    Article  Google Scholar 

  17. Ai H, Flask C, Weinberg B, et al. Magnetite-loaded polymeric micelles as ultrasensitive magnetic-resonance probes. Adv Mater, 2005, 17: 1949–1952

    Article  Google Scholar 

  18. Dubertret B, Skourides P, Norris D J, et al. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science, 2002, 298: 1759–1762

    Article  Google Scholar 

  19. Gao X, Cui Y, Levenson R M, et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol, 2004, 22: 969–976

    Article  Google Scholar 

  20. Nouvel C, Dubois P, Dellacherie E, et al. Silylation reaction of dextran: effect of experimental conditions on silylation yield, regioselectivity, and chemical stability of silylated dextrans. Biomacromolecules, 2003, 4: 1443–1450

    Article  Google Scholar 

  21. Bajgai M P, Aryal S, Lee D R, et al. Physicochemical characterization of self-assembled poly(epsilon-caprolactone) grafted dextran nanoparticles. Colloid Polym Sci, 2008, 286: 517–524

    Article  Google Scholar 

  22. Ydens I, Rutot, D, Degee, P, et al. Controlled synthesis of poly (epsilon-caprolactone)-grafted dextran copolymers as potential environmentally friendly surfactants. Macromolecules, 2000, 33: 6713–6721

    Article  Google Scholar 

  23. Xie J, Peng S, Brower, N, et al. One-pot synthesis of monodisperse iron oxide nanoparticles for potential biomedical applications. Pure Appl Chem, 2006, 78: 1003–1014

    Article  Google Scholar 

  24. Josephson, L, Lewis J, Jacobs P, et al. The effects of iron oxides on proton relaxivity. Magn Reson Imaging, 1988, 6: 647–653

    Article  Google Scholar 

  25. Ditsch A, Laibinis P E, Wang D I C, et al. Controlled clustering and Enhanced tability of olymer-oated agnetic anoparticles. Langmuir, 2005, 21: 6006–6018

    Article  Google Scholar 

  26. Berret J F, Schonbeck N, Gazeau F, et al. Controlled clustering of superparamagnetic nanoparticles using block copolymers: Design of new contrast agents for magnetic resonance imaging. J Am Chem Soc, 2006, 128: 1755–1761

    Article  Google Scholar 

  27. Koenig S H, Kellar K E. Theory of 1/T 1 and 1/T 2 NMRD profiles of solutions of magnetic nanoparticles. Magn Reson Med, 1995, 34: 227–233

    Article  Google Scholar 

  28. Aguirre D A, Behling C A, Alpert, E, et al. Liver fibrosis: Noninvasive diagnosis with double contrast material-enhanced MR imaging. Radiology, 2006, 239: 425–437

    Article  Google Scholar 

  29. Kato N, Ihara S, Tsujimoto T, et al. Effect of resovist on rats with different severities of liver cirrhosis. Invest Radiol, 2002, 37: 292–298

    Article  Google Scholar 

  30. Reimer P, Balzer T. Ferucarbotran (Resovist): A new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: Properties, clinical development, and applications. Eur Radiol, 2003, 13: 1266–1276

    Google Scholar 

  31. Wang Y X, Hussain S M, Krestin G P. Superparamagnetic iron oxide contrast agents: Physicochemical characteristics and applications in MR imaging. Eur Radiol, 2001, 11: 2319–2331

    Article  Google Scholar 

  32. Kim S H, Choi D, Lim H K, et al. Detection of hepatic VX2 carcinomas with ferucarbotran-enhanced magnetic resonance imaging in rabbits: Comparison of nine pulse sequences. Eur J Radiol, 2006, 59: 413–423

    Article  Google Scholar 

  33. Reimer P, Muller M, Marx C, et al. Evaluation of the time window for Resovist-enhanced T2-weighted MRI of the liver. Academic radiology, 2002, 9 (Suppl 2): 336–338

    Article  Google Scholar 

  34. Weissleder R, Hahn P F, Stark D D, et al. Superparamagnetic iron oxide: enhanced detection of focal splenic tumors with MR imaging. Radiology, 1998, 169: 399–403

    Google Scholar 

  35. Shamsi K, Balzer T, Saini S, et al. Superparamagnetic iron oxide particles (SH U 555 A): Evaluation of efficacy in three doses for hepatic MR imaging. Radiology, 1998, 206: 365–371

    Google Scholar 

  36. Van Beers B E, Sempoux C, Materne R, et al. Biodistribution of ultrasmall iron oxide particles in the rat liver. J Magn Reson Imaging, 2001, 13: 594–599

    Article  Google Scholar 

  37. Moghimi S M, Hunter A C, Murray J C. Long-circulating and target- specific nanoparticles: theory to practice. Pharmacol Rev, 2001, 53: 283–31

    Google Scholar 

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Correspondence to Hua Ai.

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Contributed equally to this work

Supported by the Program for New Century Excellent Talents in University (Grant No. NCET-06-0781), Distinguished Young Scholars Project of Sichuan Province (Grant No. 06ZQ026-007), National Natural Science Foundation of China (Grant Nos. 30570514, 50603015 & 50830107) and National Basic Research Program of China (Grant No. 2005CB623903)

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Wang, Q., Su, H., Xia, C. et al. Amphiphilic dextran/magnetite nanocomposites as magnetic resonance imaging probes. Chin. Sci. Bull. 54, 2925–2933 (2009). https://doi.org/10.1007/s11434-009-0255-7

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  • DOI: https://doi.org/10.1007/s11434-009-0255-7

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