Dipartimento di Scienza e Tecnologia del Farmaco

Descrizione del progetto

Members of other units:

Federica Maione (I.R.C.C. Candiolo, Torino)
Patrick Couvreur (UMR CNRS 8612, Institut Galien Paris-Sud, Faculté Pharmacie Paris-Sud, France)

Sponsors:
Local funds (ex_60%) University of Torino  
University of Paris Sud 

Description
The covalent linkage of a squalene tail to drugs provides amphiphilic bioconjugates which spontaneously self-organize into nanoassemblies in water. The first molecule linked to squalene was the anticancer agent gemcitabine. Then, the property of amphiphilic squalenoyl conjugates to form nanoparticles was extended to other anticancer agents, such as doxorubicine and paclitaxel, to antiviral drugs, such as acyclovir, and to probes, such as ruthenium complexes. Another squalene derivative was synthesized and added to squalene anticancer nanoparticles to obtain actively targeted drug delivery systems. This compound anchors to the nanoparticles with the squalene chain and, through a hydrophobic spacer, it is able to link on the nanoparticle surface a targeting agent (i.e. a peptide) that specifically recognizes cancer cells. Works are in progress to encapsulate an iron oxide magnetic nanocore to obtain actively targeted theranostic particles.

References:
- Couvreur P., Stella B., Reddy L.H., Hillaireau H., Dubernet C., Desmaële D., Lepêtre-Mouelhi S., Rocco F., Dereuddre-Bosquet N., Clayette P., Rosilio V., Marsaud V., Renoir J.-M., Cattel L. (2006) Nano Letters 6 (11), 2544-2548.
- Dosio F., Reddy L.H., Ferrero A., Stella B., Cattel L., Couvreur P. (2010) Bioconj Chem 21 (7), 1349-1361.
- Stella B., Arpicco S., Rocco F., Burgalassi S., Nicosia N., Tampucci S., Chetoni P., Cattel L. (2012) Eur J Pharm Biopharm 80, 39-45.
- Dosio F., Stella B., Ferrero A., Garino C., Zonari D., Arpicco S., Cattel L., Giordano S., Gobetto R. (2013) Int J Pharm 440 (2), 221-228.

Keywords:
Squalenoylation, Nanoassemblies, Bioconjugates, Anticancer drugs, Antiviral drugs