使用类似蛋白质的分子架构进行向药物递送
Evonne M Rezler1, David R Khan, Janelle Lauer-Fields
1Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, Florida 33431, USA.
Journal of the American Chemical Society
|April 3, 2007
概括
使用类两性蛋白的向性脂质体显示出药物输送的前景. 这些基于纳米技术的药物递送系统 (nanoDDSs) 选择性地向转移性黑色素瘤细胞上的CD44/素硫酸蛋白糖 (CSPG) 受体.
科学领域:
- 生物技术和纳米医学
- 材料科学 材料科学 材料科学
- 细胞生物学 细胞生物学
背景情况:
- 基于纳米技术的药物递送系统 (nanoDDS) 为向治疗提供了增强的物理,化学和生物特性.
- 在转移性黑色素瘤中,CD44/冠状素硫酸盐蛋白质甘油 (CSPG) 受体过度表达,从而成为选择性药物输送的标.
- 在IV型原体内确定了CD44/CSPG的结合序列,使得有针对性的连接体设计成为可能.
研究的目的:
- 构建和评估氨基基 (PA) 功能化脂质体,以向向CD44/CSPG受体提供向输送.
- 研究脂质体脂质组成对稳定性和准效率的影响.
- 评估转移性黑色素瘤和纤维细胞细胞系中PA-脂质体的细胞吸收和向特异性.
主要方法:
- 合成一种设计用于结合CD44/CSPG的三螺旋-两 (alpha1(IV) 1263-1277 PA) 的合成.
- 将α1(IV) 1263-1277 PA纳入具有不同脂质组成的脂质体 (DSPC,DPPC,DSPG,DLPC,胆固醇) 中.
- 通过竞争性抑制试验评估脂质体稳定性,细胞光体输送和受体介导吸收.
主要成果:
- 与DPPC相比,由DSPC,DSPG和胆固醇组成的脂质体表现出更大的稳定性.
- 阿尔法1(IV) 1263-1277 PA增强了DPPC脂质体的稳定性,并证明了选择性光向CD44/CSPG表达细胞的输送.
- 向特异性得到证实,在外源性alpha1 ((IV) 1263-1277.1263-1277.IV) 的预化后,化物输送的剂量依赖性下降.
结论:
- 可合理设计和微调用于药物输送应用的胺氨基基向脂质体.
- 脂质体脂质组成显著影响系统的稳定性和性能.
- alpha1(IV) 1263-1277 PA脂质体显示出作为针对CD44/CSPG阳性转移性黑色素瘤的向纳米DDS的潜力.
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