科研之友
微信
新浪微博
Facebook
分享链接
摘要
A redox-sensitive drug delivery system was fabricated. Dendritic poly (L-glutamic acid) was synthesized. Anti-tumor drug methotrexate (MTX) was immobilized on the dendritic poly(L-glutamic acid) via disulfide bonds using cystines as linkers. The disulfide bond was sensitive to glutathione in intracellular environment,thus to release the MTX from the dendritic poly (L-glutamic acid) backbones. The dendrite: poly(L-glutamic acid) backbones and drug loaded conjugates were characterized by nuclear magnetic resonance (NMR). The release profiles of the conjugates were investigated in phosphate buffer saline (PBS) with dithiothreitol (DTT) to simulate the intracellular environment; the results showed that the release rates were closely dependant on the concentration of DTT. Higher DTT concentration resulted in faster release. When the concentration was lower titan 0.2 mmol/L. MTX was riot released front dendritic backbones. The conjugates were incubated with HepG2 cells to evaluate their anti-tumor effect in vitro. The dendritic poly(L-glutamic acid) was nontoxic to cells even when its concentration was as high as 20 mu g/mL. The inhibition effect of the conjugates on tumor cells was better than that of free MTX after incubation for 72 h. Fluorescein isothiocyanate (FITC) was immobilized on the dendrmers and conjugates to trace the endocytosis. The MTX could promote the cell uptake for its folic acid mimetic structure.
- 出版日期2011-8-20
- 单位四川大学
