Novel Polymer−DNA Hybrid Polymeric Micelles Composed of Hydrophobic Poly(<scp>d</scp>,<scp>l</scp>-lactic-<i>co</i>-glycolic Acid) and Hydrophilic Oligonucleotides

Abstract

Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) was chemically conjugated to oligonucleotide (ODN) to form an amphiphatic structure which is similar to an A-B type block copolymer. A terminal end of PLGA was activated and reacted with primary amine-terminated ODN. The ODN/PLGA conjugates self-assembled in aqueous solution to form a micellar structure by serving PLGA segments as a hydrophobic core and ODN segments as a surrounding hydrophilic corona. Critical micelle concentration was determined by a spectroflurometric method. Atomic force microscopic observation revealed that the micelle size was around 80 nm. These micelles could release ODN in a sustained manner by controlled degradation of hydrophobic PLGA chains. Compared to unconjugated ODN, the ODN/PLGA micelles could be more efficiently transported within cells, presumably by endocytosis. This study proposes a potential delivery method of ODN into cells by forming hybrid ODN/PLGA micelles.