Improved Tumor Infiltration and Immunomodulation for Tumor Therapy: A Pathway Based on Tetrahedral Framework Nucleic Acids Coupled Bacterial Nanocells,Nano Letters

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Improved Tumor Infiltration and Immunomodulation for Tumor Therapy: A Pathway Based on Tetrahedral Framework Nucleic Acids Coupled Bacterial Nanocells
Nano Letters ( IF 9.6 ) Pub Date : 2022-11-17 , DOI: 10.1021/acs.nanolett.2c03943
Yuxi Zhan ₁ , Yuxin Zhang ₁ , Chenchen Mao ₁ , Jiajie Li ₁ , Yuxuan Zhao ₁ , Ye Chen ₁ , Zhiqiang Liu ₁ , Yunfeng Lin ₁

Affiliation

Growing evidence indicates that the tumor microenvironment (TME) can be combined with other therapeutic modalities, including cytotoxic chemotherapy and targeted therapies, to produce unanticipated results in oncology treatment. Here, we proposed a novel bacterial nanomaterial capable of targeting peritumoral biofilm and modulating TME. It was based on tetrahedral framework nucleic acids (T) that were chemically attached to aptamer AS1411 and 5-fluorouracil (AT5). Additionally, the oral pathogenic bacterium Streptococcus mutans (S.m) was employed as a biocarrier for synergetic biofilm targeting and immunomodulation. In this article, the effect of AT5-coupled S.m-derived nanocells (S.m-AT5) was investigated in vitro and in vivo. Due to bacteria aggregation in the tumor-specific biofilm, these nanocells released greater medication concentrations. Furthermore, they exerted an immunomodulatory effect by stimulating the maturation of dendritic cells (DCs) and regulation of T cells. This chemo-immunostimulation combination has a powerful antitumor impact. It may also be an advanced approach for boosting the survival rate of cancer patients.

中文翻译：

用于肿瘤治疗的改进的肿瘤浸润和免疫调节：基于四面体骨架核酸偶联细菌纳米细胞的途径

越来越多的证据表明，肿瘤微环境 (TME) 可以与其他治疗方式（包括细胞毒性化疗和靶向治疗）相结合，在肿瘤治疗中产生意想不到的结果。在这里，我们提出了一种能够靶向瘤周生物膜并调节 TME 的新型细菌纳米材料。它基于化学连接到适体 AS1411 和 5-氟尿嘧啶 (AT5) 的四面体框架核酸 (T)。此外，口腔致病菌变异链球菌(Sm) 被用作协同生物膜靶向和免疫调节的生物载体。在这篇文章中，研究了 AT5 偶联的 Sm 衍生纳米细胞 (Sm-AT5)在体外和体内的作用. 由于肿瘤特异性生物膜中的细菌聚集，这些纳米细胞释放出更高浓度的药物。此外，它们通过刺激树突状细胞 (DC) 的成熟和 T 细胞的调节发挥免疫调节作用。这种化学免疫刺激组合具有强大的抗肿瘤作用。它也可能是提高癌症患者生存率的先进方法。

更新日期：2022-11-17

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