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.

Metal-organic frameworks (MOFs) exhibit attractive properties such as highly accessible surface area, large porosity, tunable pore size, and built-in redox-active metal sites. They may serve as excellent candidates to construct implantable flexible devices for biochemical sensing due to their high thermal and solution stability. However, MOFs-based sensors have only been mostly reported for in-vitro chemical sensing, their use in implantable chemical sensing and combination with flexible electronics to achieve excellent mechanical compatibility with tissues and organs has rarely been summarized. This paper systematically reviews the biochemical sensors based on MOFs and discusses the feasibility to achieve implantable biochemical sensing through MOFs-based flexible electronics. The properties of MOFs and underlying mechanisms have been introduced, followed by a summarization of different biochemical sensing applications. Strategies to integrate MOFs with flexible devices have been supplied from the standpoints of matching mechanics and compatible fabrication processes. Issues that should be addressed in developing flexible MOFs sensors and potential solutions have also been provided, followed by the perspective for future applications of flexible MOFs sensors. This paper may serve as a reference to offer potential guidelines for the development of flexible MOFs-based biochemical sensors that may benefit future applications in personal healthcare, disease diagnosis and treatment, and fundamental study of various biological processes.