In vivo the application of optogenetic manipulation in deep tissue is seriously obstructed by the limited penetration depth of visible light that is continually applied to activate a photoactuator. Herein, we designed a versatile upconversion optogenetic nanosystem based on a blue-light-mediated heterodimerization module and rare-earth upconversion nanoparticles (UCNs). The UCNs worked as a nanotransducer to convert external deep-tissue-penetrating near-infrared (NIR) light to local blue light to noninvasively activate photoreceptors for optogenetic manipulation in vivo. In this, we demonstrated that deeply penetrating NIR light could be used to control the apoptotic signaling pathway of cancer cells in both mammalian cells and mice by UCNs. We believe that this interesting NIR-light-responsive upconversion optogenetic nanotechnology has significant application potentials for both basic research and clinical applications in vivo.

The combination of novel materials with flexible electronic technology may yield new concepts of flexible electronic devices that effectively detect various biological chemicals to facilitate understanding of biological processes and conduct health monitoring. This paper demonstrates single- or multichannel implantable flexible sensors that are surface modified with conductive metal-organic frameworks (MOFs) such as copper-MOF and cobalt-MOF with large surface area, high porosity, and tunable catalysis capability. The sensors can monitor important nutriments such as ascorbicacid, glycine, l-tryptophan (l-Trp), and glucose with detection resolutions of 14.97, 0.71, 4.14, and 54.60 × 10 m, respectively. In addition, they offer sensing capability even under extreme deformation and complex surrounding environment with continuous monitoring capability for 20 d due to minimized use of biological active chemicals. Experiments using live cells and animals indicate that the MOF-modified sensors are biologically safe to cells, and can detect l-Trp in blood and interstitial fluid. This work represents the first effort in integrating MOFs with flexible sensors to achieve highly specific and sensitive implantable electrochemical detection and may inspire appearance of more flexible electronic devices with enhanced capability in sensing, energy storage, and catalysis using various properties of MOFs.

Realizing precise control of the therapeutic process is crucial for maximizing efficacy and minimizing side effects, especially for strategies involving gene therapy (GT). Herein, a multifunctional Prussian blue (PB) nanotheranostic platform is first designed and then loaded with therapeutic plasmid DNA (HSP70-p53-GFP) for near-infrared (NIR) light-triggered thermo-controlled synergistic GT/photothermal therapy (PTT). Due to the unique structure of the PB nanocubes, the resulting PB@PEI/HSP70-p53-GFP nanoparticles (NPs) exhibit excellent photothermal properties and pronounced tumor-contrast performance in T 1 /T 2weighted magnetic resonance imaging. Both in vitro and in vivo studies demonstrate that mild NIR-laser irradiation (≈41 °C) activates the HSP70 promoter for tumor suppressor p53-dependent apoptosis, while strong NIR-laser irradiation (≈50 °C) induces photothermal ablation for cellular dysregulation and necrosis. Significant synergistic efficacy can be achieved by adjusting the NIR-laser irradiation (from ≈41 to ≈50 °C), compared to using GT or PTT alone. In addition, in vitro and in vivo toxicity studies demonstrate that PB@PEI/HSP70-p53-GFP NPs have good biocompatibility. Therefore, this work provides a promising theranostic approach for controlling combined GT and PTT via the heat-shock response.

Mechanoluminescence (ML) is characterized by photon emission under mechanical action, which is promising for biomedical applications, such as stress sensing and artificial skin. However, the use of ML in deep tissues has encountered a bottleneck due to the need for contact excitation. In this paper, a magneto‐luminescence microdevice (MLMD) is devised to realize optical emission through non‐contact excitation of a rotating magnetic field. The MLMD is composed of ML materials (lanthanide‐doped CaZnOS crystals) and a magnet bar, in which the magnet bar can collect excitation energy of the magnetic field and then drive the ML materials to emit light by rotational motion. The optical emission of the MLMD is used to remotely stimulate two optogenetic models at different tissue depths, including subcutaneous photodynamic therapy of tumor and neuromodulation of behaving mice. This work establishes an innovative approach to achieve remote control of light delivery, which is expected to inspire new applications in biomedicine.

Recombinant bacterial colonization plays an indispensable role in disease prevention, alleviation, and treatment. Successful application mainly depends on whether bacteria can efficiently spatiotemporally colonize the host gut. However, a primary limitation of existing methods is the lack of precise spatiotemporal regulation, resulting in uncontrolled methods that are less effective. Herein, we design upconversion microgels (UCMs) to convert near-infrared light (NIR) into blue light to activate recombinant light-responsive bacteria (Lresb) in vivo, where autocrine ''functional cellular glues'' made of adhesive proteins assist Lresb inefficiently colonizing the gut. The programmable engineering platform is further developed for the controlled and effective colonization of Escherichia coli Nissle 1917 (EcN) in the gut. The colonizing bacteria effectively alleviate DSS-induced colitis in mice. We anticipate that this approach could facilitate the clinical application of engineered microbial therapeutics to accurately and effectively regulate host health.