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Fusobacterium nucleatum-mimicking nanovehicles to overcome chemoresistance for breast cancer treatment by eliminating tumor-colonizing bacteria
Chem ( IF 23.5 ) Pub Date : 2024-02-23 , DOI: 10.1016/j.chempr.2024.01.030
Linfu Chen , Jingjing Shen , Zheyu Kang , Zemin Zhang , Zixuan Zheng , Lin Zhang , Zhisheng Xiao , Qiang Zhang , Huapan Fang , Jun Zhou , Yudong Wang , Yang Yang , Zhuang Liu , Qian Chen

Herein, we discovered that the tumor-colonized F. nucleatum is closely correlated with the expression of D-galactose-β(1-3)-N-acetyl-D-galactosamine (Gal-GalNAc) in breast cancer and would promote chemoresistance. Therefore, we designed F. nucleatum-mimicking nanovehicles by fusing the F. nucleatum cytoplasmic membrane (FM) with antibiotic-loaded liposomes and found that the obtained nanovehicles (Colistin-LipoFM) could selectively eradicate tumor-resident F. nucleatum and significantly restore chemotherapy efficacy. In addition, our F. nucleatum-mimicking nanovehicles, containing a broad-spectrum antibiotic, could interfere with other intratumoral microbiomes to inhibit the lung metastasis of breast cancer and further promote the efficacy of standard clinically used breast cancer chemotherapy, leading to complete regression of established tumors in some mice. Therefore, the F. nucleatum-mimicking nanovehicles should be an excellent targeted drug delivery carrier for tumors colonized with bacteria and provide a promising possibility to promote existing cancer therapies by selectively killing tumor-colonizing bacteria.



中文翻译:

模仿具核梭杆菌的纳米载体通过消除肿瘤定植细菌来克服乳腺癌治疗的化疗耐药性

在此,我们发现肿瘤定植的具核梭菌与乳腺癌中 D-半乳糖-β(1-3)-N-乙酰基-D-半乳糖胺 (Gal-GalNAc) 的表达密切相关,并会促进化疗耐药。因此,我们通过将具核梭杆菌细胞质膜(FM)与负载抗生素的脂质体融合来设计模仿具核梭杆菌的纳米载体,并发现所获得的纳米载体(Colistin-LipoFM)可以选择性地根除肿瘤驻留的具核梭杆菌并显着恢复化疗。功效。此外,我们的模拟具核梭杆菌的纳米载体含有广谱抗生素,可以干扰其他瘤内微生物群,抑制乳腺癌的肺转移,并进一步促进临床标准乳腺癌化疗的疗效,从而使乳腺癌的完全消退。在一些小鼠体内形成了肿瘤。因此,模拟具核梭菌的纳米载体应该是细菌定植肿瘤的优异靶向药物递送载体,并通过选择性杀死肿瘤定植细菌为促进现有癌症治疗提供有希望的可能性。

更新日期:2024-02-23
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