基於β-cyclodextrin-modified carboxymethyl chitosan/hyaluronic acid的交叉连接复合纳米凝作为针对抗瘤治疗的双响应载体
Xin Wang1, Shurong Zhang1, Xiaoyue Wang1
1Department of Medicinal Chemistry, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
International journal of pharmaceutics
|November 9, 2024
概括
生物降解复合纳米凝有效向瘤,并提供多克索鲁比 (DOX) 进行增强的癌症治疗. 这些纳米凝在临床前模型中显示了降低的毒性和改善的瘤抑制.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术纳米技术
- 药物输送系统 药物输送系统
- 癌症治疗方法 癌症治疗方法
背景情况:
- 纳米化药物输送系统通过瘤向增强化疗效率和安全性.
- 第一线化疗通常需要改进的输送策略,以最大限度地提高治疗结果.
- 有针对性的治疗可以减轻与常规化疗相关的全身毒性.
研究的目的:
- 开发可生物降解,瘤向的复合纳米凝,用于控制细胞内多克索鲁比 (DOX) 释放.
- 在临床前瘤模型中评估DOX载荷纳米凝的疗效和安全性.
- 调查开发的纳米凝系统的准机制和释放动力学.
主要方法:
- 采用一共价交叉连接方法,从碳甲基,氨酸,氨酸和环氧中合成纳米凝.
- 在纳米凝中加载了多克索鲁比 (DOX),并优化了它们的尺寸和药物加载能力.
- 在体外研究评估通过CD44受体介导的细胞内和DOX释放在特定的细胞内条件下 (GSH,酸性pH). 在体内有效性在4T1瘤携带的小鼠中进行了测试.
主要成果:
- 优化纳米凝的尺寸约为190nm,药物载荷能力为28.3%.
- 载有DOX的纳米凝证明了有效的内化到瘤细胞,主要是通过CD44受体介导的内细胞分裂.
- 在4T1瘤携带小鼠中观察到显著的瘤生长抑制,可观察到的副作用毒性最小,归因于主动 (CD44) 和被动 (EPR效应) 向.
结论:
- 开发的复合纳米凝代表了针对性瘤治疗的有希望的策略.
- 该系统促进受控的细胞内DOX释放,增强治疗疗效.
- 积极和被动向的组合有助于改善瘤抑制和减少全身毒性.
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