TPP-alantolactone结合物及其用于抗瘤应用的纳米治疗形式
Andrey V Nemtarev1, Mariya E Shemakhina2, Tatiana N Pashirova3
1Alexander Butlerov Institute of Chemistry, Kazan (Volga Region) Federal University, Kremlevskaya St., 18, Kazan 420008, Russia; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov St., 8, Kazan 420088, Russia.
Colloids and surfaces. B, Biointerfaces
|September 13, 2025
概括
新的三酸 (TPP) - 酸 (TPP-AL) 纳米颗粒向癌细胞线粒体,显示出强大的抗瘤和抗菌活性. 这些双作用药物为癌症和细菌感染提供了有前途的双作用治疗策略.
科学领域:
- 纳米技术和药物输送
- 线粒体向癌症治疗的治疗方法
- 抗菌剂 抗菌剂 抗菌剂
背景情况:
- 针对线粒体的药物输送对新型癌症疗法构成了挑战.
- 三基 (TPP) 基因因增强了细胞和线粒体膜的透,这是由于正电荷和疏水性.
- 将纳米技术与线粒体策略相结合,对于有效的癌症治疗至关重要.
研究的目的:
- 为了合成四次性γ-oxoalkylphosphonium盐 (TPP-alantolactone,TPP-AL) 以有针对性地输送到线粒体.
- 开发和表征与TPP-AL.修改的新型线粒体向的脂质纳米系统 (脂质体和固体脂质纳米颗粒,SLN).
- 评估TPP-AL及其纳米系统的体外细胞毒性,细胞吸收,线粒体效应和抗菌活性.
主要方法:
- 在温和条件下高产率合成TPP-alantolactone (TPP-AL).
- 制备和表征TPP-AL修饰脂质体和固体脂质纳米粒子 (TPP-AL-SLN).
- 在体外细胞毒性测试 (IC50),使用共聚焦显微镜进行细胞吸收研究,线粒体膜潜能评估,ROS产生,caspase-9表达分析和细胞周期分析.
- 抗菌活性测试,包括最低杀菌度 (MBC) 的确定.
主要成果:
- 在实验室中,TPP-AL对人类十二指腺腺癌 (HuTu 80) 细胞 (IC50 = 0.4 μM) 具有高选择性的高细胞毒性 (17.5).
- TPP-alantolactone-SLN (TPP-AL-SLN) 对M-HeLa癌细胞系显著增强了细胞毒性 (增加了多达520倍).
- TPP-AL诱导了线粒体膜脱极化,增加了ROS产量和caspase-9的过度表达,表明通过内在线粒体通路诱导了亡.
- TPP-AL对包括MRSA (MBC = 7.8μM) 在内的グラム阳性细菌表现出显著的杀菌活性,与norfloxacin相比.
结论:
- 针对线粒体的TPP-AL修饰纳米系统 (脂质体和SLN) 是癌症治疗的有效药物输送平台.
- TPP-AL通过内在线粒体途径触发亡,并表现出作为抗瘤和抗菌剂的双重作用.
- 这些由TPP衍生的酸乳装饰的纳米系统具有针对性癌症治疗和对抗细菌感染的巨大潜力.
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