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Letter

Squalenoyl Nanomedicines as Potential Therapeutics

Supporting Info

Patrick Couvreur,*^† Barbara Stella,^†^‡ L. Harivardhan Reddy,^† Hervé Hillaireau,^† Catherine Dubernet,^† Didier Desmaële,^§ Sinda Lepêtre-Mouelhi,^§ Flavio Rocco,^‡ Nathalie Dereuddre-Bosquet, Pascal Clayette, Véronique Rosilio,^† Véronique Marsaud,^† Jack-Michel Renoir,^† and Luigi Cattel^‡

Univ. Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8612, IFR 141, 92296 Châtenay-Malabry Cedex, France, Università degli Studi di Torino, Facoltà di Farmacia, Dipartimento di Scienza e Tecnologia del Farmaco, 10125 Torino, Italy, Univ. Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8076 Biocis, 92296 Châtenay-Malabry Cedex, France, and SPI-BIO, Laboratoire de Neurovirologie, CEA, 92265 Fontenay-aux-Roses Cedex, France

Nano Lett., 2006, 6 (11), pp 2544–2548

DOI: 10.1021/nl061942q

Publication Date (Web): October 7, 2006

Corresponding author. E-mail: patrick.couvreur@cep.u-psud.fr.

†

Univ. Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8612, IFR 141.

‡

Università degli Studi di Torino, Facoltà di Farmacia, Dipartimento di Scienza e Tecnologia del Farmaco.

Univ. Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8076.

‖

SPI-BIO, Laboratoire de Neurovirologie, CEA.

Abstract

Nucleoside analogues display significant anticancer or antiviral activity by interfering with DNA synthesis. However, there are some serious restrictions to their use, including their rapid metabolism and the induction of resistance. We have discovered that the linkage of nucleoside analogues to squalene leads to amphiphilic molecules that self-organize in water as nanoassemblies of 100−300 nm, irrespective of the nucleoside analogue used. The squalenoyl gemcitabine exhibited superior anticancer activity in vitro in human cancer cells and gemcitabine-resistant murine leukemia cells, and in vivo in experimental leukemia both after intravenous and oral administration. The squalenoylation of other antiretroviral nucleosides also led to more potent drugs when tested in primary cultures of HIV-infected lymphocytes. Thus, the squalenoylation is an original technology platform for generating more potent anticancer and antiviral nanomedicines.

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