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Polymerized mixed aggregates containing gadolinium complex and CCK8 peptide

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Abstract

Two novel amphiphilic unimers containing an aliphatic hydrophobic chain (PDA) with two C≡C triple bonds and hydrophilic heads presenting the chelating agent DTPAGlu and the CCK8 bioactive peptide, respectively, have been prepared by solid phase synthesis. Aggregates obtained by mixing together PDA-DTPAGlu, or its Gd(III) complex, and PDA-L2-CCK8 in 70/30 molar ratio before and after a polymerization process carried out by UV irradiation have been structurally characterized by means of small angle neutron scattering. The relaxivity properties of aggregates containing Gadolinium complexes have also been investigated. Elongated mixed micelles have been observed, in which the relaxivity value r 1p for each Gadolinium complex, measured at 20 MHz and 298 K, is around 12 mM–1 s–1.

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References

  1. Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333 Oak Brook, IL, United States

    CAS  Google Scholar 

  2. Aime S, Cabella C, Colombatto S, Geninatti Crich S, Gianolio E, Maggioni F (2002) Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J Magn Reson Imaging Field 16:394–406

    Article  Google Scholar 

  3. Aime S, Fasano M, Terreno E, Botta M (2001) Protein-bound metal chelates. In: Merbach A, Toth E (eds) Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging. Wiley, New York, pp 193–241

    Google Scholar 

  4. Gao J, Nasongkla N, Khemtong C (2007) cRGD-encoded, MRI-visible polymeric micelles for tumor-targeted drug delivery. In: Amiji M (ed) Nanotechnology for Cancer Therapy. CRC, Boca Raton, pp 465–475 1 plate

    Google Scholar 

  5. Accardo A, Tesauro D, Roscigno P, Gianolio E, Paduano L, D'Errico G, Pedone C, Morelli G (2004) Physicochemical properties of mixed micellar aggregates containing CCK peptides and Gd complexes designed as tumor-specific contrast agents in MRI. J Am Chem Soc 126:3097–3107

    Article  CAS  Google Scholar 

  6. Accardo A, Tesauro D, Morelli G, Gianolio E, Aime S, Vaccaro M, Mangiapia G, Paduano L, Schillen K (2007) High-relaxivity supramolecular aggregates containing peptides and Gd complexes as contrast agents in MRI. JBIC, J Biol Inorg Chem 12:267–276

    Article  CAS  Google Scholar 

  7. Tesauro D, Accardo A, Gianolio E, Paduano L, Teixeira J, Schillen K, Aime S, Morelli G (2007) Peptide derivatized lamellar aggregates as target-specific MRI contrast agents. ChemBioChem 8:950–955

    Article  CAS  Google Scholar 

  8. Vaccaro M, Mangiapia G, Paduano L, Gianolio E, Accardo A, Tesauro D, Morelli G (2007) Structural and relaxometric characterization of peptide aggregates containing gadolinium complexes as potential selective contrast agents in MRI. ChemPhysChem 8:2526–2538

    Article  CAS  Google Scholar 

  9. Evans DF (1998) The colloidal domain: where physics, chemistry, biology, and technology meet, 2nd edn. Wiley, New York

    Google Scholar 

  10. Zou G, Fang K, Xia S, He P (2002) Elasticity of 10,12-pentacosadiynoic acid monolayer and the polymerized monolayer at varying pH and temperatures. Langmuir 18:6602–6605

    Article  CAS  Google Scholar 

  11. Reubi JC, Schaer J-C, Waser B (1997) Cholecystokinin (CCK)-A and CCK-B/gastrin receptors in human tumors. Cancer Res 57:1377–1386

    CAS  Google Scholar 

  12. Anelli PL, Fedeli F, Gazzotti O, Lattuada L, Lux G, Rebasti F (1999) L-Glutamic acid and L-lysine as useful building blocks for the preparation of bifunctional DTPA-like ligands. Bioconjug Chem 10:137–140

    Article  CAS  Google Scholar 

  13. Chan WC, White PD (2000) Basic procedures. Fmoc Solid Phase Peptide Synthesis. Oxford University Press, Oxford, pp 41–76

    Google Scholar 

  14. Edelhoch H (1967) Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry 6:1948–1954

    Article  CAS  Google Scholar 

  15. Pace CN, Vajdos F, Fee L, Grimsley G, Gray T (1995) How to measure and predict the molar absorption coefficient of a protein. Protein Sci Field 4:2411–2423

    CAS  Google Scholar 

  16. Birdi KS, Singh HN, Dalsager SU (1979) Interaction of ionic micelles with the hydrophobic fluorescent probe 1-anilino-8-naphthalenesulfonate. J Phys Chem 83:2733–7

    Article  CAS  Google Scholar 

  17. De Vendittis E, Palumbo G, Parlato G, Bocchini V (1981) A fluorimetric method for the estimation of the critical micelle concentration of surfactants. Anal Biochem 115:278–286

    Article  Google Scholar 

  18. Lakowicz JR (1983) Principles of Fluorescence Spectroscopy. Springer, New York

    Google Scholar 

  19. Wignall GD, Bates FS (1987) Absolute calibration of small-angle neutron scattering data. J Appl Crystallogr 20:28–40

    Article  CAS  Google Scholar 

  20. Russell TP, Lin JS, Spooner S, Wignall GD (1988) Intercalibration of small-angle x-ray and neutron scattering data. J Appl Crystallogr 21:629–638

    Article  CAS  Google Scholar 

  21. Shinoda K, Nakagawa T, Tamamushi B, Isemura T (1962) Colloidal Surfactants, Some Physicochemical Properties. Academy, New York

    Google Scholar 

  22. Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium(III) Chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev (Washington, D. C.) 99:2293–2352

    CAS  Google Scholar 

  23. Lipari G, Szabo A (1982) Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity. J Am Chem Soc 104:4546–4559

    Article  CAS  Google Scholar 

  24. Lipari G, Szabo A (1982) Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 2. Analysis of experimental results. J Am Chem Soc 104:4559–4570

    Article  CAS  Google Scholar 

  25. Torres S, Martins JA, Andre JP, Geraldes CFGC, Merbach AE, Toth E (2006) Supramolecular assembly of an amphiphilic GdIII chelate: Tuning the reorientational correlation time and the water exchange rate. Chem–Eur J 12:940–948

    CAS  Google Scholar 

  26. Nicolle GM, Toth E, Eisenwiener K-P, Macke HR, Merbach AE (2002) From monomers to micelles: investigation of the parameters influencing proton relaxivity. JBIC, J Biol Inorg Chem 7:757–769

    Article  CAS  Google Scholar 

  27. Nicolle GM, Tóth É, Schmitt-Willich H, Radchel B, Merbach AE (2002) The impact of rigidity and water exchange on the relaxivity of a dendritic MRI contrast agent. Chem - Eur J 8:1040–1048

    Article  CAS  Google Scholar 

  28. Kotlarchyk M, Chen SH (1983) Analysis of small angle neutron scattering spectra from polydisperse interacting colloids. J Chem Phys 79:2461–2469

    Article  CAS  Google Scholar 

Download references

Acknowledgements

LP, MV, GMa wish to thank CSGI and MIUR (PRIN-2006) for funding the research. Some of us (MV, LP, GMa) wish to thank the Forschungszentrum Jülich for the provision of the beam time for SANS measurements. The SANS experiments were supported by the European Commission, NMI3 contract RII3-CT-2003-505925. GMo, AA, DT thank the European Molecular Imaging Laboratories Network (EMIL) and the Italian Consortium CIRCMSB for financial support.

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Authors and Affiliations

  1. Dipartimento di Chimica-CSGI, Università degli Studi di Napoli “Federico II”, via Cinthia, 80126, Naples, Italy

    Mauro Vaccaro, Gaetano Mangiapia & Luigi Paduano

  2. Dipartimento di Scienze Biologiche-CIRPeB, Università degli Studi di Napoli “Federico II”, via Mezzocannone 16, 80134, Naples, Italy

    Antonella Accardo, Diego Tesauro & Giancarlo Morelli

  3. Dipartimento di Chimica I.F.M., Unversità di Torino, Via P. Giuria 7, 10125, Turin, Italy

    Eliana Gianolio

  4. Jülich Centre for Neutron Science, Forschungszentrum Jülich GmbH, Lichtenbergstrasse 1, 85747, Garching bei München, Germany

    Henrich Frielinghaus

  5. CSGI—Consorzio interuniversitario per lo sviluppo dei Sistemi a Grande Interfase, Florence, Italy

    Mauro Vaccaro, Gaetano Mangiapia & Luigi Paduano

Authors
  1. Mauro Vaccaro
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  2. Gaetano Mangiapia
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  3. Antonella Accardo
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  4. Diego Tesauro
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  5. Eliana Gianolio
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  6. Henrich Frielinghaus
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  7. Giancarlo Morelli
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  8. Luigi Paduano
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Correspondence to Giancarlo Morelli or Luigi Paduano.

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Vaccaro, M., Mangiapia, G., Accardo, A. et al. Polymerized mixed aggregates containing gadolinium complex and CCK8 peptide. Colloid Polym Sci 286, 1643–1652 (2008). https://doi.org/10.1007/s00396-008-1940-9

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  • DOI: https://doi.org/10.1007/s00396-008-1940-9

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