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Journal of Neural Transmission

, Volume 118, Issue 1, pp 145–153 | Cite as

NIR-labeled nanoparticles engineered for brain targeting: in vivo optical imaging application and fluorescent microscopy evidences

  • G. TosiEmail author
  • L. Bondioli
  • B. Ruozi
  • L. Badiali
  • G. M. Severini
  • S. Biffi
  • A. De Vita
  • B. Bortot
  • D. Dolcetta
  • F. Forni
  • M. A. Vandelli
Basic Neurosciences, Genetics and Immunology - Original Article

Abstract

The presence of the blood–brain barrier (BBB) makes extremely difficult to develop efficacious strategies for targeting contrast agents and delivering drugs inside the Central Nervous System (CNS). To overcome this drawback, several kinds of CNS-targeted nanoparticles (NPs) have been developed. In particular, we proposed poly-lactide-co-glycolide (PLGA) NPs engineered with a simil-opioid glycopeptide (g7), which have already proved to be a promising tool for achieving a successful brain targeting after i.v. administration in rats. In order to obtain CNS-targeted NPs to use for in vivo imaging, we synthesized and administrated in mice PLGA NPs with double coverage: near-infrared (NIR) probe (DY-675) and g 7. The optical imaging clearly showed a brain localization of these novel NPs. Thus, a novel kind of NIR-labeled NPs were obtained, providing a new, in vivo detectable nanotechnology tool. Besides, the confocal and fluorescence microscopy evidences allowed to further confirm the ability of g 7 to promote not only the rat, but also the mouse BBB crossing.

Keywords

Nanoparticles NIR Optical imaging Confocal and fluorescence microscopy Brain targeting 

Notes

Acknowledgments

The authors thank Luca Fabiani for microtome cut, Dr. Stefania Bettelli for the help in DAPI staining and Andrea Lorenzon for animal preparation. We also thank Prof. Luca Costantino for the synthesis of g7-PLGA polymer and Dr. Andrea Tombesi, CIGS (Centro Interdipartimentale Grandi Strumenti) of the University of Modena and Reggio Emilia for assistance in confocal analysis. This work is supported by Azzurra, Associazione Malattie Rare O.N.L.U.S.

References

  1. Bandettini PA (2009) What’s new in neuroimaging methods? Ann NY AcadSci 1156:260–293CrossRefGoogle Scholar
  2. Brambilla D, Nicolas J, Le Droumaguet B, Andrieux K, Marsau V, Couraud PO, Couvreur P (2010) Design of fluorescently tagged poly(alkyl cyanoacrylate) nanoparticles for human brain endothelial cell imaging. Chem Commun 46:2602–2604CrossRefGoogle Scholar
  3. Costantino L, Gandolfi F, Tosi G, Rivasi F, Vandelli MA, Forni F (2005) Peptide-derivatized biodegradable nanoparticles able to cross the blood–brain barrier. J Control Rel 108:84–96CrossRefGoogle Scholar
  4. Costantino L, Gandolfi F, Bossy-Nobs L, Tosi G, Gurny R, Rivasi F, Vandelli MA, Forni F (2006) Nanoparticulate drug carriers based on hybrid poly(d,l-lactide-co-glycolide)-dendron structures. Biomaterials 26:4635–4645CrossRefGoogle Scholar
  5. Dhanasekaran M, Palian M, Alves I, Yeomans L, Keyari CM, Davis P, Bilsky EJ, Egleton RD, Yamamura HI, Jacobsen NE, Tollin G, Hruby VJ, Porreca F, Polt R (2005) Glycopeptides related to b-endorphines adopt helical amphipathic conformation in the presence of lipid bilayers. J Am Chem Soc 127:5435–5448PubMedCrossRefGoogle Scholar
  6. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S (1989) Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm 55:R1–R4CrossRefGoogle Scholar
  7. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R (1994) Biodegradable long-circulating polymeric nanospheres. Science 263:1600–1603PubMedCrossRefGoogle Scholar
  8. Hillman EMC (2007) Optical brain imaging in vivo: techniques and applications from animal to man. J Biomed Opt 12(051402):1–28Google Scholar
  9. Hu R, Yong KT, Roy I, Ding H, Law WC, Cai H, Zhang X, Vathy LA, Bergey EJ, Prasad PN (2010) Functionalized near-infrared quantum dots for in vivo tumor vasculature imaging. Nanotechnology 21. doi: 10.1088/0957-4484/21/14/145105
  10. Inoue Y, Izawa K, Kiryu S, Tojo A, Ohtomo K (2008) Diet and abdominal autofluorescence detected by in vivo fluorescence imaging of living mice diet. Mol Imaging 7:21–27PubMedGoogle Scholar
  11. Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538PubMedCrossRefGoogle Scholar
  12. Polt R (2005) Glycosylated neuropeptides: a new vista for neuropharmacology? Med Res Rev 25:557–585PubMedCrossRefGoogle Scholar
  13. Polt R, Palian MM (2001) Glycopeptide analgesics. Drugs Future 26:561–576CrossRefGoogle Scholar
  14. Prilloff S, Fan J, Henrich-Noack P, Sabel BA (2010) In vivo confocal neuroimaging (ICON): non-invasive, functional imaging of the mammalian CNS with cellular resolution. Eur J Neurosci 31:521–528PubMedCrossRefGoogle Scholar
  15. Tanisaka H, Kizaka-Kondoh S, Makino A, Tanaka S, Hiraoka M, Kimura S (2008) Near-infrared fluorescent labeled peptosome for application to cancer imaging. Bioconj Chem 19:109–117CrossRefGoogle Scholar
  16. Tosi G, Rivasi F, Gandolfi F, Costantino L, Vandelli MA, Forni F (2005) Conjugated poly(d, l-lactide-co-glycolide) for the preparation of in vivo detectable nanoparticles. Biomaterials 26:4189–4195PubMedCrossRefGoogle Scholar
  17. Tosi G, Costantino L, Rivasi F, Ruozi B, Leo E, Vergoni AV, Tacchi R, Bertolini A, Vandelli MA, Forni F (2007) Targeting the central nervous system. In vivo experiments with peptide derivatized nanoparticles loaded with loperamide and rhodamine 123. J Control Rel 122:1–9CrossRefGoogle Scholar
  18. Tosi G, Vergoni AV, Ruozi B, Bondioli L, Badiali L, Rivasi F, Costantino L, Forni F, Vandelli MA (2010) Sialic acid and glycopeptides conjugated PLGA nanoparticles for central nervous system targeting: in vivo pharmacological evidence and biodistribution. J Control Rel 145:49–57CrossRefGoogle Scholar
  19. Vergoni AV, Tosi G, Tacchi R, Vandelli MA, Bertolini A, Costantino L (2009) Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution. Nanomedicine 5:369–377Google Scholar
  20. Wang ZH, Wang ZY, Suna CS, Wang CY, Jianga TY, Wang SL (2010) Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain. Biomaterials 31:908–915PubMedCrossRefGoogle Scholar
  21. Xu Z, Pilch DS, Srinivasan AR, Olson WK, Geacintov NE, Breslauer KJ (1997) Modulation of nucleic acid structure by ligand binding induction of a DNA-RNA-DNA hybrid triplex by DAPI intercalation. Bioorg Med Chem 5:1137–1147PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • G. Tosi
    • 1
    Email author
  • L. Bondioli
    • 1
  • B. Ruozi
    • 1
  • L. Badiali
    • 1
  • G. M. Severini
    • 2
  • S. Biffi
    • 3
  • A. De Vita
    • 1
  • B. Bortot
    • 2
  • D. Dolcetta
    • 4
  • F. Forni
    • 1
  • M. A. Vandelli
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.Department of Molecular Medicine and LaboratoryInstitute of Maternal and Child Health IRCCS Burlo GarofoloTriesteItaly
  3. 3.Optical Imaging LaboratoryCBM, Area Science ParkTriesteItaly
  4. 4.Mauro Baschirotto Institute for Rare DiseasesB.I.R.D. FoundationVicenzaItaly

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