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双重准和生物响应纳米-PROTAC诱导精确有效的肺癌治疗

Xiaoling Guan¹, Xiaowei Xu¹, Yiwen Tao¹

¹The Fifth Affiliated Hospital, The Affiliated Panyu Central Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, The School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China.

Journal of nanobiotechnology

|November 10, 2024

概括

一种新型的纳米-PROTAC (RLDPB) 通过向含原蛋白4 (BRD4) 降解来增强肺癌治疗. 这种双重准,生物响应纳米粒子改善了药物输送和瘤回归,提供了一个新的治疗途径.

科学领域:

在瘤学瘤学.
纳米技术纳米技术
生物化学生物化学

背景情况:

表观遗传失调是肺癌的一个关键因素.
像DBET6这样的蛋白质溶解向嵌合体 (PROTAC) 试剂通过降解含有原蛋白的蛋白质4 (BRD4) 显示出潜在的降解潜力.
目前的PROTACs的局限性包括低组织特异性和生物可用性,阻碍了肺癌的临床转化.

研究的目的:

开发一种双准,生物响应的纳米-PROTAC (RLDPB) 以改善肺癌治疗.
为了提高PROTAC剂dBET6.6的输送和有效性.
克服传统PROTACs在肺癌治疗中的局限性.

主要方法:

构建了一个纳米-PROTAC (RLDPB) 使用pH/氨酸 (GSH) 响应的二硫化物键结合的多酸 (DS-PLGA) 来加载dBET6.
伪装的纳米颗粒具有同型的LLC细胞膜和结合的cRGD配体,用于双重准.
评估了体外细胞吸收,体内瘤积累和治疗疗效,包括诱导亡和BRD4降解.

主要成果:

RLDPB显示肺癌细胞增强细胞吸收和瘤积累.
pH/GSH反应性促进了dBET6在癌细胞内的有效释放.
通过BRD4降解,RLDPB有效诱导肺癌细胞亡和瘤回归.

结论:

开发的纳米-PROTAC,RLDPB,显示出作为肺癌治疗策略的巨大潜力.
双重向和生物响应性提高了PROTAC的输送和抗瘤功效.
RLDPB代表了基于PROTAC的肺癌治疗的有希望的进步.

关键词:

生物响应性生物响应性双重定位是双重的目标.肺癌是一种肺癌.这就是PROTAC.的 dBET6 值.

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