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Moreover, through molecular engineering (including increasing covalent anchoring sites and steric hindrance groups of cyanine dyes), FSNP-C exhibits the highest fluorescent intensity both in water solution (12.3-fold improvement compared to free dye) and living cells due to the limitation of molecular motion. Thus, this study provides an effectively strategy by combining a local hydrophobic cage and molecular engineering for NIR FSNPs in long-term bright fluorescence imaging and a stable PDT process.The cellulosome is a supramolecular multienzymatic protein complex that functions as a biological nanomachine of cellulosic biomass degradation. How the megadalton-size cellulosome adapts to a solid substrate is central to its mechanism of action and is also key for its efficient use in bioconversion applications. We report time-lapse visualization of crystalline cellulose degradation by individual cellulosomes from Clostridium thermocellum by atomic force microscopy. Upon binding to cellulose, the cellulosomes switch to elongated, even filamentous shapes and morph these dynamically at below 1 min time scale according to requirements of the substrate surface under attack. Compared with noncomplexed cellulases that peel off material while sliding along crystalline cellulose surfaces, the cellulosomes remain bound locally for minutes and remove the material lying underneath. The consequent roughening up of the surface leads to an efficient deconstruction of cellulose nanocrystals both from the ends and through fissions within. Distinct modes of cellulose nanocrystal deconstruction by nature's major cellulase systems are thus revealed.Increasing accumulation and retention of nanomedicines within tumor tissue is a significant challenge, particularly in the case of brain tumors where access to the tumor through the vasculature is restricted by the blood-brain barrier (BBB). This makes the application of nanomedicines in neuro-oncology often considered unfeasible, with efficacy limited to regions of significant disease progression and compromised BBB. However, little is understood about how the evolving tumor-brain physiology during disease progression affects the permeability and retention of designer nanomedicines. We report here the development of a modular nanomedicine platform that, when used in conjunction with a unique model of how tumorigenesis affects BBB integrity, allows investigation of how nanomaterial properties affect uptake and retention in brain tissue. By combining different in vivo longitudinal imaging techniques (including positron emission tomography and magnetic resonance imaging), we have evaluated the retention of nanorlier stages of the disease. Importantly, these results provide a more predictive approach for designing efficacious personalized nanomedicines based on a particular patient's condition.In this work, we brought together two existing clinical techniques used in cancer treatment-X-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially targeted biodegradable polymer poly(lactic-co-glycolic acid) nanocarriers incorporating a photosensitizer verteporfin, ultrasmall (2-5 nm) gold nanoparticles as radiation enhancers, and triphenylphosphonium acting as the mitochondrial targeting moiety. The average size of the nanocarriers was about 160 nm. Upon X-ray radiation our nanocarriers generated cytotoxic amounts of singlet oxygen within the mitochondria, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells. Our X-PDT strategy effectively controlled tumor growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. In vivo data indicate that our X-PDT treatment is cytoreductive, antiproliferative, and profibrotic. buy NSC697923 The nanocarriers induce radiosensitization effectively, which makes it possible to amplify the effects of radiation. A radiation dose of 4 Gy combined with our nanocarriers allows equivalent control of tumor growth as 12 Gy of radiation, but with greatly reduced radiation side effects (significant weight loss and resultant death).The amount of charge of a material has always been regarded as a property (or state) of materials and can be measured precisely and specifically. This study describes for the first time a fundamental physical-chemical phenomenon in which the amount of charge of a material is actually a variable-it depends on the shape of the material. Materials are shown to have continuously variable and reversible ranges of charge states by changing their shapes. The phenomenon was general for different shapes, transformations, materials, atmospheric conditions, and methods of charging. The change in charge was probably due to a dynamic exchange of charge from the material to the surrounding atmosphere as the shape changed via the reversible ionization and deposition of air molecules. Similar changes in charge were observed for self-actuating materials that changed their shapes autonomously. This fundamental relationship between geometry and electrostatics via chemistry is important for the broad range of applications related to the charge of flexible materials.The recently discovered CRISPR-Cas gene editing system and its derivatives have found numerous applications in fundamental biology research and pharmaceutical sciences. The need for precise external control over the gene editing and regulatory events has driven the development of inducible CRISPR-Cas systems. While most of the light-controllable CRISPR-Cas systems are based on protein engineering, we developed an alternative synthetic approach based on modification of crRNA/tracrRNA duplex (guide RNA or gRNA) with photocaging groups, preventing the gRNA from recognizing its genome target sequence until its deprotection is induced within seconds of illumination. This approach relies on a straightforward solid-phase synthesis of the photocaged gRNAs, with simpler purification and characterization processes in comparison to engineering a light-responsive protein. We have demonstrated the feasibility of photocaging of gRNAs and light-mediated DNA cleavage upon brief exposure to light in vitro. We have achieved light-mediated spatiotemporally resolved gene editing as well as gene activation in cells, whereas photocaged gRNAs showed virtually no detectable gene editing or activation in the absence of light irradiation.
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