Jeong J H, Park T G
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.
Bioconjug Chem. 2001 Nov-Dec;12(6):917-23. doi: 10.1021/bc010052t.
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.
可生物降解的聚（D，L-乳酸-共-乙醇酸）（PLGA）与寡核苷酸（ODN）进行化学偶联，形成一种类似于A-B型嵌段共聚物的两亲结构。PLGA的末端被活化，并与伯胺末端的ODN反应。ODN/PLGA共轭物在水溶液中自组装，通过将PLGA链段作为疏水核心，ODN链段作为周围的亲水冠层，形成胶束结构。通过荧光光谱法测定临界胶束浓度。原子力显微镜观察表明，胶束尺寸约为80nm。这些胶束可以通过疏水PLGA链的可控降解以持续的方式释放ODN。与未偶联的ODN相比，ODN/PLGA胶束可能通过内吞作用更有效地在细胞内运输。本研究提出了一种通过形成混合ODN/PLGA胶束将ODN递送至细胞的潜在方法。
