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具有pH敏感的瘤热带主义混合膜涂层纳米颗粒用于重编程瘤微环境并增强抗瘤免疫力

Jie Zhang¹, Liwen Wei², Xiaocao Ma²

¹Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P R China.

Acta biomaterialia

|May 30, 2023

概括

这项研究开发了一种新的纳米平台 (HM-BPT),通过抑制谷氨酸代谢来重编程瘤免疫微环境 (TIME). HM-BPT有效地抑制了瘤生长并增强了抗癌免疫反应,显示了组合癌症治疗的前景.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
癌症研究癌症研究

背景情况:

代谢失调是癌症发展和瘤免疫微环境 (TIME) 的关键驱动因素,阻碍了有效的化疗和免疫治疗.
针对代谢重编程提供了一个有希望的癌症治疗策略,但药物溶解性问题限制了对固体瘤的有效性.

研究的目的:

开发一个多功能生物模拟纳米平台 (HM-BPT) 用于针对性地输送一种谷氨酸代谢抑制剂 (BPTES) 来重新编程 TIME.
在4T1异种移植模型中评估HM-BPT的治疗疗效,重点关注瘤抑制和免疫调节.

主要方法:

使用pH敏感的瘤热带性混合膜涂层的氧化物 (MnO2) 纳米颗粒封装BPTES,构建HM-BPT.
利用来自间干细胞膜 (MSCm) 和pH敏感脂质体 (pSL) 的混合膜用于TME向和内/溶酶体逃逸.
在体内评估HM-BPT对瘤生长,免疫细胞透 (CTLs),巨细胞极化 (M1),STING通路激活,谷氨 (GSH) 枯竭和氧气 (O2) 供应的影响.

主要成果:

在4T1异种移植模型中,HM-BPT表现出了显著的瘤抑制.
用HM-BPT治疗显著增加了细胞毒性T淋巴细胞 (CTL) 透,并促进了巨细胞的M1表型再极化.
HM-BPT激活了STING通路,耗尽了GSH,并提供了O2,通过改善免疫抑制时间来协同增强抗瘤免疫反应.

结论:

开发的HM-BPT纳米平台有效地重新编程瘤免疫微环境并激活抗瘤免疫力.
通过克服现有治疗方法的局限性,HM-BPT显示出作为增强癌症联合治疗的治疗策略的巨大潜力.
这项研究为TME代谢重编程和免疫激活提供了一个有希望的纳米平台,为耐火性恶性瘤提供了希望.

关键词:

癌症组合疗法是癌症的综合疗法.代谢重编程是一种代谢重编程.刺痛是一种刺痛.瘤的热带性瘤的热带性对于pH值敏感的物质

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