Biomedical Microdevices

, 11:1187 | Cite as

Influence of PEG chain on the complement activation suppression and longevity in vivo prolongation of the PCL biomedical nanoparticles

  • Xiaoqian Shan
  • Yuan Yuan
  • Changsheng Liu
  • Xinyi Tao
  • Yan Sheng
  • Feng Xu


The process of opsonization is the major biological barrier to the injectable polymeric nanoparticles (NPs). Complement protein is one kind of opsonins and it can be activated potentially by the negative charged particles. The fragment C3b generated by complement activation could subsequently induce the opsonization on the NPs surface. The aim of our work was to examine the relationship between the hydrophilic poly(ethylene glycol) (PEG) chain on the surface of NPs and particles longevity in vivo from the biological point of view such as complement activation (C3 cleavage) as well as uptake by macrophages. The studies showed that the introduction of PEG chains led to slightly smaller NPs with lower polydispersities than those prepared from naked poly(ε-caprolactone) (PCL) and enhanced the ζ potential of NPs from −27.17 mV to −6.046 mV. It was also found that PEG hydrophilic chain could decrease the C3 cleavage and remarkably suppress opsonization and phagocytosis subsequently. In biodistribution investigations in vivo, as a control, PCL NPs were present in MPS tissues in the first 5 min followed by metabolism elimination rapidly, whereas the PEGylated NPs had more particles blood retention in vivo after injection. In fact, in present work, it has been convinced that these results in vivo could be predicted by the in vitro fluorescent phagocytosis model and the extent of complement activation in advance.


PEGylation NPs Prolong longevity in vivo Biodistribution Complement activation 


  1. Y.J. Teramura, H. Kanazawa, H. Sakai, S. Takeoka, E. Tsuchida, Bioconjugate. Che 14, 1171 (2003)CrossRefGoogle Scholar
  2. F.J. Lou Carmichael, Transfusion and Apheresis Science 24, 17 (2001)CrossRefGoogle Scholar
  3. T.M.S. Chang, Trends Biotechnol 17, 61 (1999)CrossRefGoogle Scholar
  4. A. Vadapalli, G. Goldman, A.S. Popel, Art. Cells., Blood Subs., and Immob. Biotech 30, 157 (2002)CrossRefGoogle Scholar
  5. K. Sou, B. Goins, S. Takeoka, E. Tsuchida, W.T. Phillips, Biomaterials 28, 2655 (2007)CrossRefGoogle Scholar
  6. E. Chambers, S. Mitragotri. J. Control. Release. 100, 111 (2004)CrossRefGoogle Scholar
  7. C. Yague, M. Moros, V. Grazu, M. Arruebo, J. Santamarıa, Chem. Eng. J 137, 45 (2008)CrossRefGoogle Scholar
  8. G. Storm, S.O. Belliot, T. Daemen, D.L. Danilo, Adv. Drug. Deliv. Rev. 17, 31 (1995)CrossRefGoogle Scholar
  9. S.M. Moghimi, S.S. Davis, Crit. Rev. Ther. Drug. Carr. Syst. 11, 31 (1994)Google Scholar
  10. A.L. Klibanov, K. Maruyama, A.M. Beckerleg, V.P. Torchilin, L. Huang, Biochim. Biophys. Acta 1062(2), 1991 (1991)Google Scholar
  11. S.H. Lee, Z. Zhang, S.S. Feng, Biomaterials 28, 2041 (2007)CrossRefGoogle Scholar
  12. H. Carstensen, R.H. Muller, B.W. Muller, Clin. Nutr. 11, 289 (1992)CrossRefGoogle Scholar
  13. Y. Dong, S.S. Feng, Biomaterials 25, 2843 (2004)CrossRefGoogle Scholar
  14. R. Voss, M.A. Brook, J. Thompson, Y. Chen, R.H. Pelton, J.D. Brennan, J. Mater. Chem. 17, 4854 (2007)CrossRefGoogle Scholar
  15. K. Ogawara, K. Furumoto, Y. Takakura, M. Hashida, K. Higaki, T. Kimura, J. Control. Release 77, 191 (2001)CrossRefGoogle Scholar
  16. S.M. Moghimi, A.C. Hunter, J.C. Murray, Pharmacol. Rev 53(2), 283 (2001)Google Scholar
  17. A. Sato, S.W. Choi, M. Hirai, A. Yamayoshi, R. Moriyama, T. Yamano, M. Takagi, A. Kano, A. Shimamoto, A. Maruyama, J. Control. Release 122, 209 (2007)CrossRefGoogle Scholar
  18. V.P. Torchilin, Pharm. Res 24, 1 (2007)CrossRefGoogle Scholar
  19. J. Zhao, C.S. Liu, Y. Yuan, X.Y. Tao, X.Q. Shan, Y. Sheng, F. Wu. Biomaterials 28, 1414 (2007)CrossRefGoogle Scholar
  20. X.Q. Shan, C.S. Liu, Y. Yuan, F. Xu, X.Y.Tao, Y. Sheng, H.J. Zhou, Colloids Surf.B: Biointerfaces (2009) doi:10.1016/j.colsurfb.2009.04.017
  21. R.K. Kainthan, M. Gnanamani, M. Ganguli, T. Ghosh, D.E. Brooks, S. Maiti, J.N. Kizhakkedathu, Biomaterials 27, 5377 (2006)CrossRefGoogle Scholar
  22. V.C.F. Mosqueira, P. Legrand, J.L. Morgat, M. Vert, E. Mysiakine, R. Gref, J.P. Devissaguet, G. Barratt, Pharm. Res 18(10), 1411 (2001a)CrossRefGoogle Scholar
  23. V.C.F. Mosqueira, P. Legrand, A. Gulik, O. Bourdon, R. Gref, D. Denis Labarre, G. Barratt, Biomaterials 22, 2967 (2001b)CrossRefGoogle Scholar
  24. E. Cenni, D. Granchi, S. Avnet, C. Fotia, M. Salerno, D. Micieli, M.G. Sarpietro, R. Pignatello, F. Castelli, N. Baldini. Biomaterials 29, 1400 (2008)Google Scholar
  25. I. Hamad, A.C. Hunter, J. Szeheni, S.M. Moghimi, Mol. Immuno 46, 225 (2008)CrossRefGoogle Scholar
  26. K.Y. Win, S.S. Feng, Biomaterials 26, 2713 (2005)CrossRefGoogle Scholar
  27. A. Vonarbourg, C. Passirani, P. Saulnier, J.P. Benoit, Biomaterials 27, 4356 (2006)CrossRefGoogle Scholar
  28. T. Okuda, S. Kawakami, T. Maeie, T. Niidome, F. Yamashita, M. Hashida, J. Control. Release 114, 69 (2006)CrossRefGoogle Scholar
  29. Y.P. Li, Y.Y. Pei, X.Y. Zhang, Z.H. Gu, Z.H. Zhou, W.F. Yuan, J.J. Zhou, J.H. Zhu, X.J. Gao, J.Control. Release 71, 203 (2001)CrossRefGoogle Scholar
  30. S.M. Moghimi, A.C. Hunter, Pharmaceut. Res 18, 1 (2001)CrossRefGoogle Scholar
  31. J.K. Gbadamosi, A.C. Hunter, S.M. Moghimi, FEBS. Lett 532, 338 (2002)CrossRefGoogle Scholar
  32. I. Bekersky, R.M. Fielding, D.E. Dressler, J.W. Lee, D.N. Buell, T.J. Walsh, Antimicrob. Agents. Chemother 46(3), 828 (2002)CrossRefGoogle Scholar
  33. M.T. Peracchia, E. Fattal, D. Desmaele, M. Besnard, J.P. Noel, J.M. Gomis, M. Appel, J. d’Angelo, P. Couvreur, J. Control. Release 60, 121 (1999a)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Xiaoqian Shan
    • 1
    • 2
  • Yuan Yuan
    • 3
  • Changsheng Liu
    • 1
    • 2
  • Xinyi Tao
    • 1
  • Yan Sheng
    • 3
  • Feng Xu
    • 1
  1. 1.The State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiPeople’s Republic of China
  2. 2.Key Laboratory for Ultrafine Materials of Ministry of EducationEast China University of Science and TechnologyShanghaiPeople’s Republic of China
  3. 3.Engineering Research Center for Biomedical Materials of Ministry of EducationEast China University of Science and TechnologyShanghaiPeople’s Republic of China

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