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Nano Research 2023, 16(2): 2829-2839 https://doi.org/10.1007/s12274-022-4963-5
Research Article | Issue | Published: 07 December 2022

A micro-nano optogenetic system based on probiotics for in situ host metabolism regulation

Show Author's Information Xinyu Zhang1,§,  Ning Ma1,§,  Wei Ling2,§,  Gaoju Pang1,  Tao Sun3,  Jing Liu1,  Huizhuo Pan1,  Meihui Cui1,  Chunli Han1,  Chun Yang1,  Jin Chang1,  Xian Huang2( ),  Hanjie Wang1( )
School of Life Sciences, Tianjin University, Tianjin 300072, China
School of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin 300072, China
School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, China

§ Xinyu Zhang, Ning Ma, and Wei Ling contributed equally to this work.

Keywords:
optogenetics, upconversion nanoparticles, synthetic biology, microelectronics, diabetics
Topics:
Synthetic biology
Cite this article:
Zhang X, Ma N, Ling W, et al. A micro-nano optogenetic system based on probiotics for in situ host metabolism regulation. Nano Research, 2023, 16(2): 2829-2839. https://doi.org/10.1007/s12274-022-4963-5
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Abstract Full text Electronic supplementary material About this article

Genetically engineered bacteria have aroused attention as micro-nano drug delivery systems in situ. However, conventional designs of engineered bacteria usually function constantly or autonomously, which might be non-specific or imprecise. Therefore, designing and optimizing in situ control strategy are important methodological progress for therapeutic researches of intestinal engineered bacteria. Here, a micro-nano optogenetic system based on probiotic was developed combining microelectronics, nanotechnology, and synthetic biology to achieve in situ controllable drug delivery. Firstly, optogenetic engineered Lactococcus lactis was orally administrated in the intestinal tract. A wearable optical device was designed to control optical signals remotely. Then, L. lactis could be customized to secrete peptides according to optical signals. As an example, optogenetic L. lactis system can be constructed to secrete glucagon-like peptide-1 (GLP-1) under the control of the wearable optical device to regulate metabolism. To improve the half-life of GLP-1 in vivo, Fc-domain fused GLP-1 was optimally used. Using this strategy, blood glucose, weight, and other features were well controlled in rats and mice models. Furthermore, upconversion microcapsules were introduced to increase the excitation wavelength of the optogenetic system for better penetrability. This strategy has biomedical potential to expand the toolbox for intestinal engineered bacteria.


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Abstract
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Electronic supplementary material
About this article

A micro-nano optogenetic system based on probiotics for in situ host metabolism regulation

Show Author's information Xinyu Zhang1,§, Ning Ma1,§, Wei Ling2,§, Gaoju Pang1, Tao Sun3, Jing Liu1, Huizhuo Pan1, Meihui Cui1, Chunli Han1, Chun Yang1, Jin Chang1, Xian Huang2( ), Hanjie Wang1( )
School of Life Sciences, Tianjin University, Tianjin 300072, China
School of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin 300072, China
School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, China

§ Xinyu Zhang, Ning Ma, and Wei Ling contributed equally to this work.

Abstract

Genetically engineered bacteria have aroused attention as micro-nano drug delivery systems in situ. However, conventional designs of engineered bacteria usually function constantly or autonomously, which might be non-specific or imprecise. Therefore, designing and optimizing in situ control strategy are important methodological progress for therapeutic researches of intestinal engineered bacteria. Here, a micro-nano optogenetic system based on probiotic was developed combining microelectronics, nanotechnology, and synthetic biology to achieve in situ controllable drug delivery. Firstly, optogenetic engineered Lactococcus lactis was orally administrated in the intestinal tract. A wearable optical device was designed to control optical signals remotely. Then, L. lactis could be customized to secrete peptides according to optical signals. As an example, optogenetic L. lactis system can be constructed to secrete glucagon-like peptide-1 (GLP-1) under the control of the wearable optical device to regulate metabolism. To improve the half-life of GLP-1 in vivo, Fc-domain fused GLP-1 was optimally used. Using this strategy, blood glucose, weight, and other features were well controlled in rats and mice models. Furthermore, upconversion microcapsules were introduced to increase the excitation wavelength of the optogenetic system for better penetrability. This strategy has biomedical potential to expand the toolbox for intestinal engineered bacteria.

Keywords: optogenetics, upconversion nanoparticles, synthetic biology, microelectronics, diabetics

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Publication history
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Acknowledgements

Publication history

Received: 26 May 2022
Revised: 25 August 2022
Accepted: 25 August 2022
Published: 07 December 2022
Issue date: February 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was sponsored by the National Science Fund for Excellent Young Scholars (No. 32122047), the National Key Research and Development Program of China (No. 2019YFA0906500), the National Natural Science Foundation of China (Nos. 31971300 and 51873150), the Key project of Tianjin Foundational Research (JingJinJi) Program, China (No. 19JCZDJC64100), the Key Research and Development Program of Tianjin (No. 19YFZCSY00190), and the National Science Foundation of Tianjin (No. 20YDTPJC00090).

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