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光控细菌代谢物用于癌症治疗。

Optically-controlled bacterial metabolite for cancer therapy.

机构信息

Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, China.

出版信息

Nat Commun. 2018 Apr 26;9(1):1680. doi: 10.1038/s41467-018-03233-9.

Abstract

Bacteria preferentially accumulating in tumor microenvironments can be utilized as natural vehicles for tumor targeting. However, neither current chemical nor genetic approaches alone can fully satisfy the requirements on both stability and high efficiency. Here, we propose a strategy of "charging" bacteria with a nano-photocatalyst to strengthen their metabolic activities. Carbon nitride (CN) is combined with Escherichia coli (E. coli) carrying nitric oxide (NO) generation enzymes for photo-controlled bacterial metabolite therapy (PMT). Under light irradiation, photoelectrons produced by CN can be transferred to E. coli to promote the enzymatic reduction of endogenous NO to cytotoxic NO with a 37-fold increase. In a mouse model, CN loaded bacteria are perfectly accumulated throughout the tumor and the PMT treatment results in around 80% inhibition of tumor growth. Thus, synthetic materials-remodeled microorganism may be used to regulate focal microenvironments and increase therapeutic efficiency.

摘要

细菌优先聚集在肿瘤微环境中,可以被用作肿瘤靶向的天然载体。然而,现有的化学或遗传方法都不能完全满足稳定性和高效性的双重要求。在这里,我们提出了一种“给”细菌充电纳米光催化剂的策略,以增强其代谢活性。氮化碳(CN)与携带一氧化氮(NO)生成酶的大肠杆菌(E. coli)结合,用于光控细菌代谢物治疗(PMT)。在光照射下,CN 产生的光电子可以转移到 E. coli 上,促进内源性 NO 的酶还原为细胞毒性的 NO,其效率增加了 37 倍。在小鼠模型中,负载 CN 的细菌在整个肿瘤中得到了很好的聚集,PMT 治疗使肿瘤生长抑制率达到 80%左右。因此,合成材料重塑的微生物可用于调节焦点微环境并提高治疗效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6458/5920064/3e73902edb9d/41467_2018_3233_Fig1_HTML.jpg

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