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通过调节免疫抑制微环境以MMP-2敏感和nHA/GNE联合封装的水凝来增强黑色素瘤治疗

Zhu Chen¹, Hongfeng Wu², Yifu Wang³

¹National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, Nanchong Hospital Beijing AnZhen Hospital, North Sichuan Medical College, Nanchong 637000, China.

Acta biomaterialia

|September 6, 2024

概括

这项研究开发了一种新的水凝,通过调节瘤微环境来治疗黑色素瘤. 水凝释放纳米酸 (nHA) 和乳酸脱酶A抑制剂 (GNE),有效抑制瘤生长并增强抗瘤免疫力.

科学领域:

生物材料科学生物材料科学
癌症治疗癌症治疗
免疫学免疫学免疫学

背景情况:

免疫抑制性瘤微环境 (TME),以乳酸和矩阵金属蛋白酶 (MMPs) 的过度表达为特征,阻碍了有效的癌症治疗.
制定调节TME的策略对于提高治疗结果至关重要,特别是在黑色素瘤治疗中.

研究的目的:

为增强黑色素瘤治疗设计一种TME调节水凝.
为了利用纳米酸 (nHA),乳酸脱酶A抑制剂 (R) -GNE-140 (GNE) 和一种MMP-2敏感的协同作用.

主要方法:

通过4臂聚乙烯糖醇-化物 (4臂-PEG-MAL) 和MMP-2敏感 (CC-14) 的反应制造水凝.
在水凝矩阵内同时封装nHA和GNE.
在体外和体内研究,以评估水凝降解,药物释放,抗黑色素瘤疗效和免疫细胞透.

主要成果:

水凝表现出pH (6.8) 和MMP-2反应,导致在模拟的TME条件下加速释放nHA和GNE.
实验室研究表明抑制黑色素瘤细胞增殖,细胞循环停止,诱导亡,减少迁移和攻击性.
在体内研究显示显著抑制瘤生长,增加CD8+T细胞和抗原呈现细胞的透,降低T调控细胞,将"冷"瘤转化为"热"瘤.

结论:

开发的TME调节水凝显示显著的希望,作为有效的黑色素瘤治疗的有效策略.
结合TME调制的nHA和GNE的协同作用,为克服黑色素瘤治疗耐药性的新方法提供了新的方法.

关键词:

免疫调节水凝是一种免疫调节水凝.免疫抑制的微环境黑色素瘤是一种黑色素瘤.纳米-氧亚帕提特是一种纳米-氧亚帕提特.

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