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一个对氧化还原反应的纳米系统,通过向STAT3来抑制耐化学性肺癌

Qiyi Feng¹, Jie Chen¹, Jinxing Huang¹

¹Department of Pulmonary and Critical Care Medicine, Precision Medicine Center, Huaxi MR Research Center (HMRRC), Frontiers Science Center for Disease-Related Molecular Network, National Clinical Research Center for Geriatrics, Department of Respiratory Medicine, and Department of Radiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

Journal of controlled release : official journal of the Controlled Release Society

|September 25, 2023

概括

这项研究开发了新的纳米粒子,以提供BBI608,一种有效的癌症干细胞 (CSC) 抑制剂,用于治疗非小细胞肺癌 (NSCLC). 这些纳米颗粒改善了药物输送,并显示出对抗化学耐药NSCLC和CSCs的优异抗瘤疗效.

科学领域:

在瘤学瘤学.
纳米医学是一种纳米医学.
癌症生物学癌症生物学

背景情况:

癌症干细胞 (CSCs) 驱动瘤开始,复发和治疗失败在非小细胞肺癌 (NSCLC).
BBI608通过抑制信号转换器和转录3激活器 (STAT3) 来向CSC,显示出对抗耐化学性NSCLC的潜力.

研究的目的:

开发BBI608的刺激响应纳米配方,以提高其生物可用性和瘤积累,用于治疗耐化学性NSCLC.
在临床前NSCLC模型中评估BBI608装载纳米颗粒的疗效和作用机制.

主要方法:

BBI608被封装成对氧化还原有反应的PEGylated分支N-(2-基) 甲基胺 (HPMA) -脱氧胆酸 (DA) 聚合纳米粒子 (BBI608-SS-NPs).
细胞毒性,增殖,迁移和体内抗瘤疗效在耐化学性NSCLC细胞系和异种移植模型 (CDX和PDX) 中进行了评估.
机理学研究研究了对STAT3和Wnt信号通路的影响.

主要成果:

BBI608-SS-NPs有效地抑制了NSCLC细胞的增殖和迁移,并专门针对高干度的CSC.
这些纳米颗粒表现出与自由BBI608相似的细胞毒性,并且在对谷氨的反应中释放了药物.
在体内,BBI608-SS-NP显示出优越的瘤积累和优越的抗瘤疗效,抑制了STAT3和Wnt通路.

结论:

响应刺激的聚合物纳米粒子提供了一个有前途的策略,用于在耐化学性NSCLC中传递BBI608.
这种纳米配方有效地向CSC并增强抗瘤活性,显示了改善NSCLC治疗的潜力.

关键词:

药物输送是药物输送的过程.药物耐药性药物耐药性药物耐药性非小细胞肺癌是非小细胞肺癌.来自患者的异种移植.在STAT3中,我们可以使用STAT3.对刺激有反应的聚合物.

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