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工程化细菌外膜囊泡重塑瘤微环境,用于增强光动力学免疫治疗

Chaofan Nie¹, Peiren Wang¹, Junru Wang¹

¹State Key Laboratory of Flexible Electronics (LoFE), Xi'an Institute of Flexible Electronics, and Xi'an Institute of Biomedical Materials and Engineering, Northwestern Polytechnical University, Xi'an, China.

Advanced healthcare materials

|December 26, 2025

概括

工程纳米疗法 (PN@OMVs) 通过结合光动力学疗法和IDO1抑制来克服瘤微环境 (TME) 抑制. 这种方法显著提高了抗瘤免疫力,并实现了高瘤抑制率,毒性最小.

科学领域:

生物医学工程生物医学工程
免疫学免疫学免疫学
纳米技术纳米技术

背景情况:

瘤免疫疗法面临来自免疫抑制瘤微环境 (TME) 的挑战,导致治疗耐药性.
现有的TME调节剂通常具有较差的溶解性和全身毒性.
外膜囊泡 (OMVs) 提供了一个潜在的药物输送平台,但需要工程来增强治疗效果.

研究的目的:

开发一个工程纳米治疗平台 (PN@OMVs) 来克服TME介导的免疫抑制.
调查光动力学疗法 (PDT) 和胺二二氧化酶1 (IDO1) 抑制在OMV中的协同效应.
在临床前癌症模型中评估PN@OMVs的疗效和安全性.

主要方法:

通过联合封装甲酸a (PPa) 和IDO1抑制剂NLG919.19的工程OMV.
用于PN@OMVs的构建,使用了由大肠杆菌BL21衍生的OMV.
在小鼠双侧皮下CT26结肠癌模型中评估PN@OMV的疗效,包括免疫细胞分析和瘤生长评估.

主要成果:

PN@OMVs显著增强了全身抗瘤免疫力,其证据是树突细胞成熟度增加 (2.77%至19.84%).
PN@OMVs有效地抑制了IDO1的活性,破坏了氨酸-氨酸路径,并减少了调节性T细胞透,逆转了TME免疫抑制.
一次PN@OMVs与光照射的单次使用,实现了92.3%的初级瘤抑制率和83.1%的远程瘤抑制率,没有可观察到的全身毒性.

结论:

工程 OMVs (PN@OMVs) 代表了协同癌症免疫治疗的有希望的平台.
PN@OMVs有效地重塑免疫抑制的TME,增强抗瘤免疫反应.
这种纳米治疗策略为改善免疫疗法的疗效和减少与治疗相关的毒性提供了潜在的解决方案.

关键词:

结肠直肠癌是什么意思免疫疗法免疫疗法在外膜囊泡中,外膜囊泡光动力学疗法是一种光动力学疗法.重塑瘤微环境的方法

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