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工程TGF-β抑制剂封装的巨体启发的多功能纳米颗粒用于联合癌症免疫治疗

Jaehyun Kim¹, Minjeong Kim¹, Seok-Beom Yong²

¹Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.

Biomaterials research

|December 19, 2023

概括

带有TGF-β抑制剂的巨细胞膜涂层纳米粒子重编程瘤微环境,提高癌症免疫治疗的有效性. 这种组合疗法显示出强大的抗癌作用和改善的免疫检查点抑制剂反应.

科学领域:

在瘤学瘤学.
纳米技术纳米技术
免疫治疗是一种免疫疗法.

背景情况:

癌症免疫疗法,就像免疫检查点抑制剂一样,在有效性和范围上都有局限性.
瘤微环境调节是改善固体瘤免疫治疗反应的关键.
转化生长因子-β (TGF-β) 通过促进M2巨细胞和癌症转移来抑制免疫治疗.

研究的目的:

开发巨细胞膜涂层的纳米粒子,装有TGF-βR1激酶抑制剂 (SD-208) 用于癌症免疫治疗.
评估抑制M2巨细胞极化和表皮细胞转化为介质细胞转化 (EMT) 的作用.
评估开发的纳米颗粒的体内治疗效果和生物分布.

主要方法:

开发载有SD-208 (M[公式:见文本]-SDNP) 的巨细胞膜涂层纳米粒子.
在体外和体内对M2巨分极和EMT抑制的评估.
生物分布研究和治疗效果评估在正位乳腺癌和转移癌症模型中.

主要成果:

M[公式:看文本]-SDNP有效抑制癌症转移,并将冷瘤转化为热瘤.
向输送和M2巨分化的阻断导致瘤中细胞毒性T淋巴细胞 (CTLs) 的增加.
与M[公式:见文本]-SDNP和抗PD-1抗体的联合治疗显示出显著的抗癌作用.

结论:

对M[公式:见文本]-SDNP和抗PD-1抗体的联合治疗大大提高了免疫治疗反应.
生物启发的纳米技术为改善癌症免疫治疗疗效提供了一个有希望的策略.
这种方法有可能成为未来针对固体瘤的治疗策略.

关键词:

癌症免疫疗法癌症免疫疗法组合疗法是一种联合疗法.免疫细胞启发的纳米粒子免疫检查点抑制剂免疫检查点抑制剂抑制TGF-β的抑制作用与瘤相关的巨细胞.

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