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-spe...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.展开更多
基金sponsored by the National Science Fund for Excellent Young Scholars(No.32122047)the National Key Research and Development Program of China(No.2019YFA0906500)+3 种基金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)the National Science Foundation of Tianjin(No.20YDTPJC00090).
文摘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.
