Squalenoyl nucleoside monophosphate nanoassemblies: new prodrug strategy for the delivery of nucleotide analogues.
4-(N)-1,1',2-trisnor-squalenoyldideoxycytidine monophosphate (SQddC-MP) and 4-(N)-1,1',2-trisnor-squalenoylgemcitabine monophosphate (SQdFdC-MP) were synthesized using phosphoramidite chemistry. These amphiphilic molecules self-assembled to about hundred nanometers size nanoassemblies in aqueous medium. Nanoassemblies of SQddC-MP displayed significant anti-HIV activity whereas SQdFdC-MP nanoassemblies displayed promising anticancer activity on leukemia cells. These results suggested that squalene conjugate of negatively charged nucleotide analogues efficiently penetrated within cells. Thus, we propose a new prodrug strategy for improved delivery of nucleoside analogues to ameliorate their biological efficacy.
Caron
Joachim
J
Université Paris-Sud, Faculté de Pharmacie, UMR CNRS 8076, 5 rue J.-B. Clément, 92296 Châtenay-Malabry, France.
Reddy
L Harivardhan
LH
Lepêtre-Mouelhi
Sinda
S
Wack
Séverine
S
Clayette
Pascal
P
Rogez-Kreuz
Christine
C
Yousfi
Rahima
R
Couvreur
Patrick
P
Desmaële
Didier
D
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013185:Squalene / Q000737:chemistry*
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D009705:Nucleosides; D011355:Prodrugs; D013185:Squalene