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可生物降解的长循环纳米激素剂优化瘤热带性化学金属免疫疗法以通过级联cGAS-STING通路激活来增强抗瘤免疫力

Hao Li¹, Cheng Zhang¹, Yue Chen¹

¹State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 211198, China.

|August 16, 2024

概括

这项研究引入了新的纳米颗粒,将化疗和免疫疗法结合起来,激活cGAS-STING通路,增强抗瘤免疫反应,以有效治疗癌症.

科学领域:

纳米技术纳米技术
免疫治疗是一种免疫疗法.
在瘤学瘤学.

背景情况:

循环GMP-AMP合成酶 (cGAS) 和干扰素基因刺激器 (STING) 途径是诱导抗瘤免疫力的有希望的目标.
瘤微环境 (TME) 通常含有免疫抑制细胞,这些细胞阻碍了cGAS-STING通路激活的有效性.
需要协同策略来克服TME介导的免疫抑制并增强免疫治疗结果.

研究的目的:

设计可生物降解的纳米颗粒用于协同化学金属免疫疗法.
为了实现cGAS-STING通路的级联激活,以增强抗瘤免疫力.
开发一种长循环,瘤向的纳米激动剂,用于癌症治疗.

主要方法:

制造Mn-doped半孔 (MM) 纳米颗粒,使用MOF封闭和红细胞膜 (eM) 伪装.
在纳米颗粒中染色 cisplatin (CDDP) 和一种 STING 激动剂 (SR-717).
在实验室和体内评估纳米粒子介导的药物释放,cGAS-STING激活和抗瘤疗效.

主要成果:

这些纳米颗粒证明了对瘤微环境刺激的反应中CDDP和SR-717的受控释放.
从癌细胞中释放的dsDNA片段触发了cGAS-STING激活,促进树突细胞成熟和细胞毒性T细胞透.
协同化学金属免疫疗法导致显著的瘤回归和增强的抗瘤免疫反应.

结论:

可生物降解,长循环的纳米颗粒有效地同时提供化疗和免疫治疗剂.
通过纳米技术的级联cGAS-STING激活为协同癌症治疗提供了一个强大的战略.
这种方法代表了结合化疗和金属免疫疗法的范式转变,用于瘤学应用.

关键词:

生物降解生物降解 cGAS-STING的激活方式癌症化学金属免疫疗法癌症化学金属免疫疗法纳米激励剂的纳米激励剂.有孔的纳米材料.

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