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用于向癌症治疗的产药结合瘤寻找共生体

Haosheng Shen^1,2,3, Changyu Zhang^4,5, Shengjie Li^1,6

¹NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore.

Nature communications

|May 21, 2024

概括

改造的植物乳杆菌 (Lactobacillus plantarum) 细菌向鼻癌 (NPC),提供强大的化疗前药物. 这种新的方法提高了药物的疗效,并显著抑制了瘤的生长,提供了一个有前途的癌症治疗策略.

科学领域:

微生物学微生物学
在瘤学瘤学.
药物输送系统药物输送系统

背景情况:

传统化疗面临的挑战是目标特异性有限.
瘤微环境中含有微生物,可以用于有针对性的前药物递送.
细菌与癌症的相互作用为癌症治疗的增强特异性提供了机会.

研究的目的:

为了设计一种细菌菌株,以有针对性地输送和激活抗癌前药物.
为了利用Lactobacillus plantarum在鼻癌 (NPC) 向的本源癌症结合性质.
通过基于微生物的输送系统来增强化疗剂的治疗疗效.

主要方法:

鉴定和设计一种具有内在癌症结合能力的Lactobacillus plantarum菌株.
对抗癌症前药物的表面加载到工程细菌上.
通过OppA介导的肝素硫酸盐识别来证明特定的NPC结合.
在NPC模型中体外和体内对前药物载荷细菌的评估.

主要成果:

工程L. plantarum通过OppA介导的识别专门与NPC细胞结合.
前代药物通过与瘤相关的生物信号被激活,在NPC附近释放SN-38.
在体外研究表明,SN-38对NPC细胞系的效能增加了10倍.
在小鼠异种移植模型中的体内研究导致67%的瘤生长抑制和54%的SN-38疗效增强.

结论:

工程化共生细菌可以实现高目标特异性,用于癌症中的前期药物输送.
这种基于微生物组的方法显著提高了化疗的效力和疗效.
这项研究提出了一种新的策略,用于开发使用细菌介导前药物递送的向癌症疗法.

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