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中性细胞上车的纳米粒子通过NETosis重编程增强了细菌介导的癌症治疗

Yuzhen Zhao¹, Mingge Li¹, Yue Guo¹

¹School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, PR China; Key Laboratory of Key Drug Preparation Technology Ministry of Education, Zhengzhou 450001, PR China.

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

|February 1, 2024

概括

工程化纳米粒子在中性粒细胞上车,以阻止NET的形成,增强沙门氏菌介导的瘤治疗,并提高抗瘤功效. 这种方法显著增加了生存率和瘤抑制.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
纳米技术纳米技术

背景情况:

减弱的沙门氏菌株在抗瘤治疗中显示出前景.
中性细胞外细胞陷 (NETs) 可以通过捕获细菌来阻碍细菌瘤治疗.
VNP20009是一种减弱的沙门氏菌株,在临床试验中已经证明了安全性.

研究的目的:

开发中性粒细胞车纳米颗粒 (SPPS) 来阻止NET形成并增强细菌介导的瘤治疗.
调查SPPS对中性粒细胞招募,NETosis和瘤内的细菌活力的影响.
通过中性粒细胞重编程评估装载siBcl-2的SPPS的协同抗瘤功效.

主要方法:

使用了4T1瘤携带的小鼠模型.
施用细菌疗法,其次是SPPS.
分析了中性粒细胞计数,SPPS瘤定位,NET水平和细菌活力.
研究了NETosis重编程和通过apoptotic体的药物再递送.

主要成果:

SPPS通过中性粒细胞的自助旅行增加了瘤的回归,大约是2.0倍.
瘤中的NETs因ROS清理介导的NETosis重编程而减少约2.0倍.
瘤中的细菌活力增加了1.9倍.
装载着siBcl-2重编程中性粒细胞的SPPS,导致药物再递送的增强和协同的抗瘤效应.

结论:

中性粒细胞车纳米粒子 (SPPS) 有效地阻断了NET的形成,增强了细菌介导的瘤疗法.
SPPS将中性粒细胞从NETosis重编程为apoptosis,促进药物再递送并提高抗瘤功效.
这种新的策略实现了大约98%的瘤抑制和90%的存活率,突出了其治疗潜力.

关键词:

药物输送是药物输送的过程.中性粒细胞外细胞陷中性粒细胞重编程中性粒细胞在搭便车旅行.通过细菌介导的瘤治疗.

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