We characterized a method to conjugate functional silver nanoparticles with vasoactive intestinal peptide (VIP), which could be used as a working model for further tailor-made applications based on VIP surface functionality. Despite sustained interest in the therapeutic applications of VIP, and the fact that its drugability could be largely improved by the attachament to functionalized metal nanoparticles, no methods have been described so far to obtain them. Materials & methods: VIP was conjugated to tiopronin-capped silver nanoparticles of a narrow size distribution, by means of proper linkers, to obtain VIP functionalized silver nanoparticles with two different VIP orientations (Ag–tiopronin–PEG–succinic–[His]VIP and Ag–tiopronin–PEG–VIP[His]). VIP intermediate nanoparticles were characterized by transmission-electron microscopy and Fourier transform infrared spectroscopy. VIP functionalized silver nanoparticles cytotoxicity was determined by lactate dehydrogenase release from mixed glial cultures prepared from cerebral cortices of 1–3 days-old C57/Bl mice. Cells were used for lipopolysaccharide stimulation at day 18–22 of culture. Results: Two different types of VIP-functionalized silver nanoparticles were obtained; both expose the C-terminal part of the neuropeptide, but in the first type VIP is attached to silver nanoparticle through its free amine terminus (Ag–tiopronin–PEG–succinic–[His]VIP), while in the second type, VIP N-terminus remains free (Ag–tiopronin–PEG–VIP[His]). VIP-functionalized silver nanoparticles did not compromise cellular viability and inhibited microglia-induced stimulation under inflammatory conditions. Conclusion: The chemical synthesis procedure developed to obtain VIP-functionalized silver nanoparticles rendered functional products, in terms of biological activity. The two alternative orientations designed, reduced the constraints for chemical synthesis that depends on the nanosurface to be functionalized. Our study provides, for the first time, a proof of principle to enhance the therapeutic potential of VIP with the valuable properties of metal nanoparticles for imaging, targeting and drug delivery.

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Published online 4 December 2009

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Acknowledgements

The authors wish to thank JM Fernandez-Santos and JC Utrilla for their guidance in immunocytochemical studies.

Financial & competing interests disclosure

The authors received financial support from the Spanish Ministry of Health (PI05/2056; PI06/1641 to D Pozo); the Andalusian Ministry of Health (PI0068 to D Pozo and PI0070 to AP Zaderenko) and the Andalusian Program for Research, Development and Innovation from the Andalusian Government (BIO323 to D Pozo; FQM319 to AP Zaderenko). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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