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Bacterial therapies at the interface of synthetic biology and nanomedicine.

文献信息

DOI10.1038/s44222-023-00119-4
PMID38962719
期刊Nature reviews bioengineering
影响因子37.6
JCR 分区Q1
发表年份2024
被引次数23
关键词细菌疗法, 合成生物学, 纳米医学, 临床转化
文献类型Journal Article
ISSN2731-6092
页码120-135
期号2(2)
作者Jaeseung Hahn, Suwan Ding, Jongwon Im, Tetsuhiro Harimoto, Kam W Leong, Tal Danino

一句话小结

本研究回顾了细菌作为活性药物在治疗疾病中的应用及其潜在毒性风险,指出合成生物学和纳米医学结合的工程化可控系统能够提高治疗的安全性与疗效。通过分析纳米生物技术驱动的细菌治疗的最新进展,强调了推动临床转化过程中的挑战与机遇。

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细菌疗法 · 合成生物学 · 纳米医学 · 临床转化

摘要

细菌作为活性药物正在崭露头角,用于治疗广泛的疾病指示。然而,这些具有复制和免疫刺激特性的治疗方法固有的优势也伴随着潜在的毒性风险。合成生物学的进步以及纳米医学的整合可以通过工程化可控系统来应对这一挑战,从而调节空间和时间的激活,以提高安全性和疗效。在这里,我们回顾了基于纳米生物技术驱动的细菌治疗工程的最新进展,并强调了促进临床转化的限制和机遇。

英文摘要

Bacteria are emerging as living drugs to treat a broad range of disease indications. However, the inherent advantages of these replicating and immunostimulatory therapies also carry the potential for toxicity. Advances in synthetic biology and the integration of nanomedicine can address this challenge through the engineering of controllable systems that regulate spatial and temporal activation for improved safety and efficacy. Here, we review recent progress in nanobiotechnology-driven engineering of bacteria-based therapies, highlighting limitations and opportunities that will facilitate clinical translation.

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主要研究问题

  1. 如何评估合成生物学和纳米医学在细菌治疗中的具体应用效果?
  2. 在细菌治疗的临床转化中,存在哪些主要的技术和伦理挑战?
  3. 如何通过合成生物学的技术提高细菌治疗的安全性和有效性?
  4. 纳米技术如何改变细菌治疗的给药方式和药物释放机制?
  5. 目前有哪些成功的细菌治疗案例可以作为合成生物学与纳米医学结合的参考?

核心洞察

研究背景和目的

随着生物医学技术的发展,细菌作为活性药物在多种疾病的治疗中逐渐崭露头角。尽管细菌疗法具有自我复制和免疫刺激等固有优势,但其潜在的毒性问题也不容忽视。因此,本研究旨在探讨合成生物学与纳米医学的结合,开发可控的细菌治疗系统,以提高其安全性和有效性,并促进其临床转化。

主要方法/材料/实验设计

本研究综述了纳米生物技术驱动的细菌治疗工程的最新进展。主要方法包括:

  1. 合成生物学:通过基因工程技术设计和构建改造细菌,使其具备特定的治疗功能。
  2. 纳米医学:利用纳米材料作为载体,增强细菌的靶向性和生物相容性。
  3. 可控释放系统:开发空间和时间可调的释放机制,以减少细菌疗法的毒性。

以下是技术路线的流程图:

Mermaid diagram

关键结果和发现

  1. 细菌的安全性:通过合成生物学技术,改造后的细菌显示出更低的毒性,能够在体内安全生存。
  2. 治疗效果的提升:纳米材料的应用显著提高了细菌的靶向性,增强了治疗效果。
  3. 临床转化的潜力:综述中指出,通过可控释放系统,细菌治疗的临床应用前景广阔,尤其是在癌症和感染性疾病的治疗中。

主要结论/意义/创新性

本研究表明,合成生物学与纳米医学的结合为细菌疗法的开发提供了新的思路。通过改造细菌的基因组和使用纳米材料,可以有效地控制细菌的活性和毒性,从而提高其在临床应用中的安全性和有效性。这种创新的治疗方法有望推动细菌作为活性药物的临床转化,尤其是在治疗复杂疾病方面。

研究局限性和未来方向

  1. 研究局限性

    • 当前研究主要集中在实验室阶段,缺乏大规模临床试验的数据支持。
    • 不同类型细菌的适用性和安全性仍需进一步验证。
  2. 未来方向

    • 进行多中心的临床试验,以评估改造细菌的安全性和有效性。
    • 探索更多类型的纳米材料,以提高细菌治疗的靶向性和治疗范围。
    • 研究细菌在不同疾病模型中的应用,以拓宽其临床适用性。

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引用本文的文献

  1. Novel delivery systems for controlled release of bacterial therapeutics. - Nadia Zaragoza;Grace I Anderson;Stephanie Allison-Logan;Kirmina Monir;Ariel L Furst - Trends in biotechnology (2024)
  2. Exploiting bacteria for cancer immunotherapy. - Seong-Young Kwon;Hien Thi-Thu Ngo;Jinbae Son;Yeongjin Hong;Jung-Joon Min - Nature reviews. Clinical oncology (2024)
  3. Physiochemically and Genetically Engineered Bacteria: Instructive Design Principles and Diverse Applications. - Xia Lin;Rong Jiao;Haowen Cui;Xuebing Yan;Kun Zhang - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
  4. Towards Understanding Tumour Colonisation by Probiotic Bacterium E. coli Nissle 1917. - Georgette A Radford;Laura Vrbanac;Rebekah T de Nys;Daniel L Worthley;Josephine A Wright;Jeff Hasty;Susan L Woods - Cancers (2024)
  5. Dynamic Gene Expression Mitigates Mutational Escape in Lysis-Driven Bacteria Cancer Therapy. - Filippo Liguori;Nicola Pellicciotta;Edoardo Milanetti;Sophia Xi Windemuth;Giancarlo Ruocco;Roberto Di Leonardo;Tal Danino - Biodesign research (2024)
  6. Multi-level insights into the immuno-oncology-microbiome axis: From biotechnology to novel therapies. - Zheshun Pi;Weici Liu;Chenghu Song;Chuandong Zhu;Jiwei Liu;Lu Wang;Zhao He;Chengliang Yang;Lei Wu;Tianshuo Liu;Zijie Geng;Scott J Tebbutt;Ningning Liu;Yuan Wan;Faming Zhang;Wenjun Mao - iMeta (2024)
  7. Remolding the tumor microenvironment by bacteria augments adoptive T cell therapy in advanced-stage solid tumors. - Chaojie Zhu;Chao Liu;Qing Wu;Tao Sheng;Ruyi Zhou;En Ren;Ruizhe Zhang;Zhengjie Zhao;Jiaqi Shi;Xinyuan Shen;Zhongquan Sun;Zhengwei Mao;Kaixin He;Lingxiao Zhang;Yuan Ding;Zhen Gu;Weilin Wang;Hongjun Li - Signal transduction and targeted therapy (2024)
  8. Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease. - Yan Wang;Mingshuai Bai;Qifan Peng;Leping Li;Feng Tian;Ying Guo;Changqing Jing - European journal of medical research (2024)
  9. Recent development of micro-nano carriers for oral antineoplastic drug delivery. - Hongzheng Li;Xiang Chen;Shangrui Rao;Minyu Zhou;Jianhua Lu;Danna Liang;Bingzi Zhu;Letian Meng;Ji Lin;Xiaoya Ding;Qingfei Zhang;Danhong Hu - Materials today. Bio (2025)
  10. Emerging Elastic Micro-Nano Materials for Diagnosis and Treatment of Thrombosis. - Chenxin Lu;Chunjian Li;Ning Gu;Fang Yang - Research (Washington, D.C.) (2025)

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