Lactosylated Poly(ethylene glycol)-siRNA Conjugate through Acid-Labile beta-Thiopropionate Linkage to Construct pH-Sensitive Polyion Complex Micelles Achieving Enhanced Gene Silencing in Hepatoma Cells

摘要

Nucleic acid medicines such as antisense DNAs and small,interfering RNAs(siRNAs)have attracted much attention as a new class of therapeutic agents.In particular,siRNAs are recently recognized as the most powerful tools for sequence-specific gene silencing via naturally occurring RNA interference(RNAi)process.Nevertheless,the therapeutic value of siRNAs under in vivo conditions is still controversial due to their low stability against enzymatic degradation,low permeability across cell membrane,and preferential liver and renal clearance.A major key to the therapeutic success of siRNA is believed to be the development of carrier systems achieving the modulated disposition in the body through the intravenous route as well as the smooth transport of intact siRNA into the interior of the target cell.