亚达曼形脚手架用于多重货物装载和细胞交付,作为β-环氧胺含量复合体
Arthi Ravi1, Atchutarao Pathigoolla1, Haripriya Balan1
1School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, Vithura, 695551, India.
Angewandte Chemie (International ed. in English)
|June 29, 2023
概括
新的阿达曼托伊德衍生物有效地与环氧素结合,使多种药物载荷能够进入细胞. 这些trioxaadamantane客体与β-cyclodextrin (β-CD) 形成稳定的复合体,增强细胞吸收和治疗疗效.
科学领域:
- 超分子化学 超分子化学
- 材料科学 材料科学 材料科学
- 纳米技术纳米技术
背景情况:
- 为治疗药物开发高效的细胞输送系统至关重要.
- 环极素 (CD) 广泛用于药物封装和输送.
- 需要能够将多个货物结合在一起的客户,以实现增强的蜂传输.
研究的目的:
- 为了合成和表征三氧亚胺衍生物作为β-cyclodextrin (β-CD) 的客体.
- 评估这些客体和β-CD之间的结合亲和力和复合形成.
- 评估用于药物输送的β-CD-guest包容复合物的生物相容性,细胞吸收和治疗疗效.
主要方法:
- 三氧亚丹衍生物的合成.
- 1H NMR定位和异热定位热量计 (ITC) 用于结合性研究.
- 单晶X射线衍射用于结构分析.
- 用于生物相容性评估的MTT测定.
- 对焦激光扫描显微镜 (CLSM) 和光激活细胞分类 (FACS) 用于细胞传递研究.
主要成果:
- 三氧亚胺衍生物与β-CD形成1:1的纳入复合体,其关联常数为~10^3 M−1.1.
- X射线衍射证实了纳入复杂结构与β-CD腔内的亚达曼坦核心.
- 对代表性客体G4及其β-CD复合体 (β-CDG4) 确定了生物相容性.
- 确认了罗达胺结合G4的细胞输送.
- G4衍生前药物 (G6和G7) 的β-CD纳入复合体显示出高效的细胞内化和载荷分布.
- 与其他配方相比,携带三个坎普托塞辛单元的β-CDG7表现出更高的细胞毒性.
结论:
- 三氧亚胺衍生物是β-CD的有效客体,使高密度货物结合成为可能.
- 这些超分子复合体有助于有效的细胞吸收和治疗剂的输送.
- 开发的阿达曼托伊德-β-CD系统对先进的药物输送应用有前途,特别是在药物负载较高的情况下.
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