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.

Nanoassemblies of squalenoyl prodrug of ddC-MP and dFdC-MP exhibit promising biological activities.Figure optionsDownload as PowerPoint slide