Novel polymer-DNA hybrid polymeric micelles composed of hydrophobic poly(D,L-lactic-co-glycolic acid) and hydrophilic oligonucleotides

Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) was chemically conju gated to oligonucleotide (ODN) to form an amphiphatic structure which is si milar 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 hydrophil ic corona. Critical micelle concentration was determined by a spectroflurom etric method. Atomic force microscopic observation revealed that the micell e size was around 80 nm. These micelles could release ODN in a sustained ma nner by controlled degradation of hydrophobic PLGA chains. Compared to unco njugated ODN, the ODN/PLGA micelles could be more efficiently transported w ithin cells, presumably by endocytosis. This study proposes a potential del ivery method of ODN into cells by forming hybrid ODN/PLGA micelles.