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Aptamer-assisted tumor localization of bacteria for enhanced biotherapy

Author

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  • Zhongmin Geng

    (Shanghai Jiao Tong University)

  • Zhenping Cao

    (Shanghai Jiao Tong University)

  • Rui Liu

    (Shanghai Jiao Tong University)

  • Ke Liu

    (Shanghai Jiao Tong University)

  • Jinyao Liu

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Weihong Tan

    (Shanghai Jiao Tong University)

Abstract

Despite bacterial-mediated biotherapies have been widely explored for treating different types of cancer, their implementation has been restricted by low treatment efficacy, due largely to the absence of tumor-specific accumulation following administration. Here, the conjugation of aptamers to bacterial surface is described by a simple and cytocompatible amidation procedure, which can significantly promote the localization of bacteria in tumor site after systemic administration. The surface density of aptamers can be easily adjusted by varying feed ratio and the conjugation is able to increase the stability of anchored aptamers. Optimal bacteria conjugated with an average of 2.8 × 105 aptamers per cell present the highest specificity to tumor cells in vitro, separately generating near 2- and 4-times higher accumulation in tumor tissue at 12 and 60 hours compared to unmodified bacteria. In both 4T1 and H22 tumor-bearing mouse models, aptamer-conjugated attenuated Salmonella show enhanced antitumor efficacy, along with highly activated immune responses inside the tumor. This work demonstrates how bacterial behaviors can be tuned by surface conjugation and supports the potential of aptamer-conjugated bacteria for both targeted intratumoral localization and enhanced tumor biotherapy.

Suggested Citation

  • Zhongmin Geng & Zhenping Cao & Rui Liu & Ke Liu & Jinyao Liu & Weihong Tan, 2021. "Aptamer-assisted tumor localization of bacteria for enhanced biotherapy," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26956-8
    DOI: 10.1038/s41467-021-26956-8
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    References listed on IDEAS

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    1. Zhenping Cao & Xinyue Wang & Yan Pang & Shanshan Cheng & Jinyao Liu, 2019. "Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Di-Wei Zheng & Ying Chen & Zi-Hao Li & Lu Xu & Chu-Xin Li & Bin Li & Jin-Xuan Fan & Si-Xue Cheng & Xian-Zheng Zhang, 2018. "Optically-controlled bacterial metabolite for cancer therapy," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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    1. Rong Sun & Mingzhu Liu & Jianping Lu & Binbin Chu & Yunmin Yang & Bin Song & Houyu Wang & Yao He, 2022. "Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Lin Li & Mengxing Zhang & Jing Li & Tiantian Liu & Qixue Bao & Xi Li & Jiaying Long & Leyao Fu & Zhirong Zhang & Shiqi Huang & Zhenmi Liu & Ling Zhang, 2023. "Cholesterol removal improves performance of a model biomimetic system to co-deliver a photothermal agent and a STING agonist for cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Huilong Luo & Yanmei Chen & Xiao Kuang & Xinyue Wang & Fengmin Yang & Zhenping Cao & Lu Wang & Sisi Lin & Feng Wu & Jinyao Liu, 2022. "Chemical reaction-mediated covalent localization of bacteria," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Zhaoting Li & Fanyi Mo & Yixin Wang & Wen Li & Yu Chen & Jun Liu & Ting-Jing Chen-Mayfield & Quanyin Hu, 2022. "Enhancing Gasdermin-induced tumor pyroptosis through preventing ESCRT-dependent cell membrane repair augments antitumor immune response," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Xiaotu Ma & Xiaolong Liang & Yao Li & Qingqing Feng & Keman Cheng & Nana Ma & Fei Zhu & Xinjing Guo & Yale Yue & Guangna Liu & Tianjiao Zhang & Jie Liang & Lei Ren & Xiao Zhao & Guangjun Nie, 2023. "Modular-designed engineered bacteria for precision tumor immunotherapy via spatiotemporal manipulation by magnetic field," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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