title: Squalenoyl nanomedicines as potential therapeutics.
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.
authors.affiliation: Univ. Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8612, IFR 141, 92296 Châtenay-Malabry Cedex, France. patrick.couvreur@cep.u-psud.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Barbara
authors.initials: B
authors.lastname: Stella
authors.forename: L Harivardhan
authors.initials: LH
authors.lastname: Reddy
authors.forename: Hervé
authors.initials: H
authors.lastname: Hillaireau
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubernet
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.forename: Sinda
authors.initials: S
authors.lastname: Lepêtre-Mouelhi
authors.forename: Flavio
authors.initials: F
authors.lastname: Rocco
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: Pascal
authors.initials: P
authors.lastname: Clayette
authors.forename: Véronique
authors.initials: V
authors.lastname: Rosilio
authors.forename: Véronique
authors.initials: V
authors.lastname: Marsaud
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007938:Leukemia / Q000188:drug therapy*; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D050997:Nanomedicine; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use*; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D051381:Rats; D013185:Squalene / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate; D014867:Water / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D009705:Nucleosides; D014867:Water; D013185:Squalene