Novel polymer-DNA hybrid polymeric micelles composed of hydrophobic poly(D,L-lactic-co-glycolic acid) and hydrophilic oligonucleotides
Novel polymer-DNA hybrid polymeric micelles composed of hydrophobic poly(D,L-lactic-co-glycolic acid) and hydrophilic oligonucleotides
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DOI：
10.1021/bc010052t
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发表时间：
2001-11-01
影响因子：
4.7
通讯作者：
Park, TG
中科院分区：
文献类型：
--
作者：
Jeong, JH;Park, TG
将可生物降解的聚（D， l -乳酸-羟基乙酸）（PLGA）与寡核苷酸（ODN）化学偶联，形成类似于A-B型嵌段共聚物的两族结构。PLGA的末端被激活并与氨基端ODN反应。ODN/PLGA在水溶液中通过偶联自组装形成胶束结构，以PLGA片段为疏水核心，ODN片段为周围亲水电晕。用荧光光谱法测定临界胶束浓度。原子力显微镜观察发现胶束尺寸在80 nm左右。这些胶束可以通过控制疏水PLGA链的降解持续释放ODN。与未偶联的ODN相比，ODN/PLGA胶束可以更有效地在细胞内运输，可能是通过内吞作用。本研究提出了一种通过形成ODN/PLGA混合胶束将ODN送入细胞的潜在方法。
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.