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结肠直肠癌的综合抗血管和免疫化疗使用响应pH的聚合物输送系统

Xiaoqian Ma¹, Qing Yang¹, Nuo Lin¹

¹State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen 361102, China.

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

|April 21, 2024

概括

这项研究开发了一种pH响应的聚合物,用于输送用于结直肠癌 (CRC) 的STING激动剂和化疗. 该系统有效地抑制了CRC的生长,并显示出协同作用的免疫化疗和抗血管作用.

科学领域:

生物材料科学生物材料科学
在瘤学瘤学.
药物运输药物运输药物运输

背景情况:

大肠直肠癌 (CRC) 是一种普遍存在的恶性瘤,需要新的治疗策略,并减少副作用.
目前的治疗方法往往缺乏特异性,并可能导致重大不良事件.

研究的目的:

设计一种对pH反应的聚合物,用于同时输送一种STING激动剂 (ASA404) 和一种用于治疗CRC的化疗剂 (HCFU).
评估这种新型药物输送系统的协同治疗效果和免疫调节效果.

主要方法:

封装ASA404和HCFU在一个响应pH的聚合物中.
在实验室中评估癌细胞的pH依赖分解和细胞毒性.
在小鼠模型中对瘤抑制,组合指数和免疫标志物水平 (TNF-α,IFN-β) 的体内评估.

主要成果:

在pH值6.37时,聚合物系统表现出pH值依赖的分解,从而实现了向药物释放.
试验室研究显示,对HCFU具有显著剂量降低指数 (DRI) 的癌细胞进行优先向 (4.09).
在体内,该系统实现了高达94.74%的瘤抑制,具有协同作用组合指数 (CI=0.41) 和TNF-α和IFN-β的血清水平增加.

结论:

一个响应pH的聚合物基的超神论平台成功地开发了CRC.
该平台展示了免疫化疗和抗血管原性疗法的结合潜力,为CRC治疗提供了一个有前途的策略,提高了疗效和降低了毒性.

关键词:

化疗化疗是一种化学疗法.结肠直肠癌是什么意思刺的路径刺的路径协同效应治疗是一种协同效应疗法.血管干扰剂是一种干扰器.

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