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通过非自然氨基酸加速细胞吸收,以抑制免疫抑制癌细胞

Meihui Yi¹, Gabriel Ashton-Rickardt¹, Weiyi Tan¹

¹Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02453, USA.

Chemistry (Weinheim an der Bergstrasse, Germany)

|March 25, 2024

概括

研究人员增强了一种类药物,以更好地向和抑制免疫抑制转移性癌细胞,包括骨肉瘤和前列腺癌. 修改后的显示出更好的细胞吸收和有效性,在癌细胞内积累,提高治疗潜力.

科学领域:

生物材料科学生物材料科学
癌症生物学癌症生物学
药物运输药物运输药物运输

背景情况:

向免疫抑制转移性癌细胞仍然是一个重大的治疗挑战.
之前的研究开发了pBP-NBD,它是一种针对转移性骨髓瘤 (mOS) 有效的,但对抵抗割的前列腺癌 (CRPC) 有中等效.

研究的目的:

为了提高pBP-NBD对CRPC和mOS细胞的疗效.
研究非自然氨基酸在改善类药物递送和细胞内积累方面的作用.

主要方法:

将非自然氨基酸L-或D-4,4'-双氨酸 (L-或D-BiP) 纳入pBP-NBD结构.
对修改后的进行mOS (Saos2,SJSA1) 和CRPC (VCaP,PC3) 细胞系的测试.
使用成像技术进行细胞吸收和细胞内定位研究.

主要成果:

带有C端阿斯巴酸甲基二聚体的D-脊柱显示出对mOS和CRPC细胞的最高活性.
与最初的pBP-NBD相比,加入BiP显著增加了细胞吸收和CRPC抑制.
组件迅速进入癌细胞,根据细胞类型积聚在细胞内网膜或溶解体中.

结论:

像BiP这样的非天然的疏水性氨基酸可以有效地增强合成的内细胞化和细胞内自我组装.
改性代表了针对和治疗免疫抑制转移性癌症的有希望的策略.
这种方法提供了一种多功能方法,可以提高基于的治疗方法的交付和疗效.

关键词:

加快了细胞吸收速度.自动组装自动组装非天然的氨基酸.

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