Showing 1 - 6 of 6 results
Optotheranostic Nanosystem with Phone Visual Diagnosis and Optogenetic Microbial Therapy for Ulcerative Colitis At-Home Care.
Ulcerative colitis (UC) is a relapsing disorder characterized by chronic inflammation of the intestinal tract. However, the home care of UC based on remote monitoring, due to the operational complexity and time-consuming procedure, restrain its widespread applications. Here we constructed an optotheranostic nanosystem for self-diagnosis and long-acting mitigations of UC at home. The system included two major modules: (i) A disease prescreening module mediated by smartphone optical sensing. (ii) Disease real-time intervention module mediated by an optogenetic engineered bacteria system. Recombinant Escherichia coli Nissle 1917 (EcN) secreted interleukin-10 (IL-10) could downregulate inflammatory cascades and matrix metalloproteinases; it is a candidate for use in the therapeutic intervention of UC. The results showed that the Detector was able to analyze, report, and share the detection results in less than 1 min, and the limit of detection was 15 ng·mL-1. Besides, the IL-10-secreting EcN treatment suppressed the intestinal inflammatory response in UC mice and protected the intestinal mucosa against injury. The optotheranostic nanosystems enabled solutions to diagnose and treat disease at home, which promotes a mobile health service development.
Upconversion optogenetic micro-nanosystem optically controls the secretion of light-responsive bacteria for systemic immunity regulation.
Chemical molecules specifically secreted into the blood and targeted tissues by intestinal microbiota can effectively affect the associated functions of the intestine especially immunity, representing a new strategy for immune-related diseases. However, proper ways of regulating the secretion metabolism of specific strains still remain to be established. In this article, an upconversion optogenetic micro-nanosystem was constructed to effectively regulate the specific secretion of engineered bacteria. The system included two major modules: (i) Modification of secretory light-responsive engineered bacteria. (ii) Optical sensing mediated by upconversion optogenetic micro-nanosystem. This system could regulate the efficient secretion of immune factors by engineered bacteria through optical manipulation. Inflammatory bowel disease and subcutaneously transplanted tumors were selected to verify the effectiveness of the system. Our results showed that the endogenous factor TGF-β1 could be controllably secreted to suppress the intestinal inflammatory response. Additionally, regulatory secretion of IFN-γ was promoted to slow the progression of B16F10 tumor.
Spatiotemporal regulation of ubiquitin-mediated protein degradation via upconversion optogenetic nanosystem.
Protein degradation technology, which is one of the most direct and effective ways to regulate the life activities of cells, is expected to be applied to the treatment of various diseases. However, current protein degradation technologies such as some small-molecule degraders which are unable to achieve spatiotemporal regulation, making them difficult to transform into clinical applications. In this article, an upconversion optogenetic nanosystem was designed to attain accurate regulation of protein degradation. This system worked via two interconnected parts: 1) the host cell expressed light-sensitive protein that could trigger the ubiquitinproteasome pathway upon blue-light exposure; 2) the light regulated light-sensitive protein by changing light conditions to achieve regulation of protein degradation. Experimental results based on model protein (Green Fluorescent Protein, GFP) validated that this system could fulfill protein degradation both in vitro (both Hela and 293T cells) and in vivo (by upconversion optogenetic nanosystem), and further demonstrated that we could reach spatiotemporal regulation by changing the illumination time (0–25 h) and the illumination frequency (the illuminating frequency of 0–30 s every 1 min). We further took another functional protein (The Nonstructural Protein 9, NSP9) into experiment. Results confirmed that the proliferation of porcine reproductive and respiratory syndrome virus (PRRSV) was inhibited by degrading the NSP9 in this light-induced system, and PRRSV proliferation was affected by different light conditions (illumination time varies from 0–24 h). We expected this system could provide new perspectives into spatiotemporal regulation of protein degradation and help realize the clinical application transformation for treating diseases of protein degradation technology.
Accurate manipulation of optogenetic proteins with wavelength tunable femtosecond laser system.
Photoactivated proteins controlled by optogenetic tools have broad application prospects in cell biology, neuroscience, and brain science. However, due to the narrow excitation wavelength width and the inflexibility of spatiotemporal operations, conventional sources such as visible light severely limit the further application of optogenetics. In this work, a femtosecond laser-operated system based on the optogenetic application was designed to address these limitations. The interaction between the photoreceptor and its partner protein can be triggered by a wavelength-tunable femtosecond laser. The results indicated that this process can be used to accurately manipulate optogenetic proteins in cells, which met spectral flexibility (700–1040 nm) and operational flexibility in time and space (a single cell to multiple cells). To demonstrate the practical applications of this process, the apoptotic signaling pathway of cancer cells was taken as an example. We believe that this wavelength-tunable femtosecond laser system will promote the development of optogenetics, making optics and even physics more powerful tools in biology.
Near-infrared light remotely up-regulate autophagy with spatiotemporal precision via upconversion optogenetic nanosystem.
In vivo noninvasively manipulating biological functions by the mediation of biosafe near infrared (NIR) light is becoming increasingly popular. For these applications, upconversion rare-earth nanomaterial holds great promise as a novel photonic element, and has been widely adopted in optogenetics. In this article, an upconversion optogenetic nanosystem that was promised to achieve autophagy up-regulation with spatiotemporal precision was designed. The implantable, wireless, recyclable, less-invasive and biocompatible system worked via two separated parts: blue light-receptor optogenetics-autophagy upregulation plasmids, for protein import; upconversion rods-encapsulated flexible capsule (UCRs-capsule), for converting tissue-penetrative NIR light into local visible blue light. Results validated that this system could achieve up-regulation of autophagy in vitro (in both HeLa and 293T cell lines) and remotely penetrate tissue (∼3.5 mm) in vivo. Since autophagy serves at a central position in intracellular signalling pathways, which is correlative with diverse pathologies, we expect that this method could establish an upconversion material-based autophagy up-regulation strategy for fundamental and clinical applications.
Near-Infrared Light Triggered Upconversion Optogenetic Nanosystem for Cancer Therapy.
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.