ABSTRACT
Antisense oligonucleotides are receiving increasing attention because of their high selectivity toward the sequence of a target mRNA. Micelle-based gene carriers exhibited a number of advantageous features for systemic delivery, including colloidal stability in solution, reduced interaction with components of biological fluid, improved in vivo pharmacokinetics, and the possibility of passive and active targeting of cancers. The intracellular pharmacokinetic behavior of the nucleic acid-based therapeutics could also be improved by employing functional polymers with the existing formulation. The susceptibility of oligodeoxynucleotide (ODN) to enzymatic digestion has been partly improved by modifying the ODN backbone with either phosphorothioate linkage or amide linkage peptide nucleic acid. The electrostatic interaction between a cationic lipid/polymer and negatively charged DNA or ODN can lead to the formation of polyelectrolyte complex nanoaggregates that can greatly facilitate cellular uptake of the polyanions by an adsorption-induced internalization process called endocytosis.
