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基于表观遗传的组合疗法和脂质体共递能通过复极化瘤相关的巨细胞来克服对奥西默提尼布耐药的NSCLC

Ting-Ting Lin^1,2, Wei Xiong^3,4, Gui-Hua Chen^2,3

¹Department of Pharmacy, Binzhou Medical University Hospital, Binzhou, 256603, China.

Acta pharmacologica Sinica

|December 19, 2023

概括

这项研究开发了一种新型的脂质体药物递送系统,将奥西默蒂尼布 (Osi) 和帕诺比诺斯塔特 (Pan) 结合起来,以克服非小细胞肺癌 (NSCLC) 的耐药性. 该疗法有效地逆转耐药性和抑制瘤生长,为NSCLC治疗提供了一个有前途的策略.

科学领域:

在瘤学瘤学.
纳米医学是一种纳米医学.
药理学药理学是指药理学的学科.

背景情况:

奥西默提尼布 (Osi) 是EGFR突变非小细胞肺癌 (NSCLC) 的一线治疗方法.
由于OSI耐药性导致患者复发的高率,需要新的治疗策略.
目前尚不完全了解Osi抵抗的潜在机制.

研究的目的:

为Osi和panobinostat (Pan) 开发一种乳酸铁素修饰的脂质体代码输送系统.
研究这种组合疗法的有效性,以克服NSCLC中的Osi耐药性.
探索潜在的作用机制,包括对瘤微环境和药物耐药性途径的影响.

主要方法:

开发一种乳酸铁素修饰的脂质体系统,用于配合输送Osi和Pan.
在体外和体内研究,以评估治疗疗效和机制.
评估与瘤相关的巨细胞 (TAM) 再极化 (M2到M1).
评价表皮层-介质细胞过渡 (EMT) 逆转和抑制糖解,乳酸生产和血管生成.

主要成果:

脂质体代码输送系统有效地输送了Osi和Pan.
组合疗法成功地将TAM从M2转向M1表型.
与表皮介质转变 (EMT) 相关的耐药性被逆转,瘤细胞糖解,乳酸生产和血管生成被抑制.
在NSCLC模型中,在克服OSI耐药性方面观察到显著的治疗效果.

结论:

Osi和Pan的脂质体共递是克服NSCLC中Osi耐药性的有效策略.
该疗法调节瘤的微环境,并逆转关键的抵抗机制.
这种方法有望改善OSI治疗耐药性NSCLC患者的临床结果.

关键词:

组合疗法治疗组合治疗.脂质体是一种脂质体.奥西默蒂尼布的耐药性是异常的这是一个Panobinostat.有针对性的药物输送.与瘤相关的巨细胞.

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