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与线粒体向功能的siBcl-2和PTX的同时递送,以克服多重药物耐药性

Liqiao Zhang¹, Xinyu Cao², Jiayi Chen²

¹Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, PR China.

International journal of pharmaceutics

|March 6, 2024

概括

这项研究开发了一种双准纳米粒子系统,以克服乳腺癌中帕克利塔塞尔 (PTX) 耐药性. 该系统连续提供小干扰性B细胞淋巴瘤-2 (siBcl-2) 和PTX,激活线粒体亡并提高化疗疗效.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
癌症治疗癌症治疗

背景情况:

对化疗,特别是对帕克利塔塞尔 (PTX) 的多药性耐药性 (MDR) 是治疗复发性和转移性乳腺癌的一个主要挑战.
由于出现PTX耐药性,现有疗法往往不足,需要新的治疗策略.

研究的目的:

开发一种双向的输送系统,用于对siBcl-2和PTX进行连续的输送,以克服PTX耐药性.
通过激活乳腺癌细胞中的线粒体亡途径来提高化疗的疗效.

主要方法:

用于瘤向和加载siBcl-2 (HFn-siBcl-2) 的重组费里丁 (HFn) 的制造.
配制HFn/siBcl-2复合物与三酸-脂质体@PTX (TL@PTX) 纳米颗粒成为HFn/siBcl-2@TL/PTX.
利用TPP介导的"质子海绵"用于siBcl-2释放和TL@PTX用于线粒体对PTX的向.

主要成果:

双重准的纳米粒子成功地将siBcl-2输送到细胞质,并将PTX输送到线粒体.
实现了Bcl-2表达的调节和线粒体亡的协同启动.
在体外和体内都证明有效抑制PTX耐药性.

结论:

开发的HFn/siBcl-2@TL/PTX系统显示出在乳腺癌中克服PTX耐药性的显著前景.
这种双重准策略为临床乳腺癌管理提供了潜在的新疗法方法.

关键词:

在HFn中,HFn是HFn 在MDR中使用MDR.线粒体的亡是线粒体的亡.在PTX PTX PTX 这就是siBcl-2的原因.

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