查看更多>>摘要：The study of the interactions of living adherent cells with mechanically stable(visco)elastic materials enables understanding and exploitation of physiological phenomena mediated by cell-extracellular communication.Insights into the interaction of cells and surrounding objects with different stability patterns upon cell contact might unveil biological responses to engineer innovative applications.Here,we hypothesize that the efficiency of cell attachment,spreading,and movement across a free-packed granular bed of microparticles depends on the microparticle diameter,raising the possibility of a necessary minimum traction force for the reinforcement of cell-particle bonds and long-term cell adhesion.The results suggest that microparticles with diameters of 14-20 μm are prone to cell-mediated mobility,holding the potential of inducing early cell detachment,while objects with diameters from 38 to 85 μm enable long-lasting cell adhesion and proliferation.An in silico hybrid particle-based model that addresses the time-dependent biological mechanisms of cell adhesion is proposed,providing inspiration for engineering platforms to address healthcare-related challenges.
查看更多>>摘要：For in vivo two-photon fluorescence microscopy(2PM) imaging,the development of techniques that can improve the observable depth and temporal resolution is an important challenge to address biological and biomedical concerns such as vascular dynamics in the deep brain(typically the hippocampal region) of living animals.Improvements have been achieved through two approaches:an optical approach using a highly tissue-penetrating excitation laser oscillating in the second near-infrared wavelength region(NIR-II,1100-1350 nm) and a chemical approach employing fluorescent probes with high two-photon brightness(characterized by the product of the two-photon absorption cross section,σ~2,and the fluorescence quantum yield,O).To integrate these two approaches,we developed a fluorescent dye exhibiting a sufficiently high σ~2 value of 68 Goeppert-Mayer units at 1100 nm.When a nanoemulsion encapsulating>1000 dye molecules per particle and a 1100 nm laser were employed for 2PM imaging,capillary blood vessels in almost the entire hippocampal CA1 region of the mouse brain(approximately 1.1-1.5 mm below the surface) were clearly visualized at a frame rate of 30 frames s~(-1)(averaged over eight frames,practically 3.75 frames s~(-1)).This observable depth and frame rate are much higher than those in previous reports on 2PM imaging.Furthermore,this nanoemulsion allowed for the visualization of blood vessels at a depth of 1.8 mm,corresponding to the hippocampal dentate gyrus.These results highlight the advantage of combining bright probes with NIR-II lasers.Our probe is a promising tool for studying the vascular dynamics of living animals and related diseases.
查看更多>>摘要：Uncontrolled and excessive fibrosis after myocardial infarction(MI) in the peri-infarct zone leads to left ventricular remodeling and deterioration of cardiac function.Inhibiting fibroblast activation during the mature phase of cardiac repair improves cardiac remodeling and function after MI.Here,we engineered a biocompatible microneedle(MN) patch using gelatin methacryloyl and loaded it with galunisertib,a transforming growth factor-beta(TGF-/i)-specific inhibitor,to treat excessive cardiac fibrosis after MI.The MN patch could sustainably release galunisertib for more than 2 weeks and provide mechanical support for the fragile ventricular wall.After being applied to a rat model of MI,the galunisertib-loaded MN patch improved long-term cardiac function and reduced cardiac fibrosis by effectively inhibiting TGF-β depending on fibroblast activation.This strategy shows the potential of the MN patch as an advanced platform to locally deliver direct antifibrotic drugs to prevent myocardial fibrosis for the treatment of Ml and the promotion of cardiac repair.
查看更多>>摘要：We have designed a new Bodipy scaffold for efficient in vivo photoacoustic(PA) imaging of nanoparticles commonly used as drug nanovectors.The new dye has an optimized absorption band in the near-infrared window in biological tissue and a low fluorescence quantum yield that leads to a good photoacoustic generation efficiency.After Bodipy-initiated ring-opening polymerization of lactide,the polylactide-Bodipy was formulated into PEGylated nanoparticles(NPs) by mixing with PLA-PEG at different concentrations.Formulated NPs around 100 nm exhibit excellent PA properties:an absorption band at 760 nm and a molar absorption coefficient in between that of molecular PA absorbers and gold NPs.Highly improved photostability compared to cyanine-labeled PLA NPs as well as innocuity in cultured macrophages were demonstrated,After intravenous injection in healthy animals,NPs were easily detected using a commercial PA imaging system and spectral unmixing,opening the way to their use as theranostic agents.
查看更多>>摘要：Rh is a noble metal introduced in bioapplications,including diagnosis and therapy,in addition to its consolidated utilization in organic catalysis and electrocatalysis.Herein,we designed the synthesis of highly crystalline Rh nanocrystal-decorated Rh-Te nanorods(RhTeNRs) through galvanic replacement of sacrificial Te nanorod(TeNR) templates and subsequent polyol regrowth.The obtained RhTeNRs showed excellent colloidal stability and efficient heat dissipation and photocatalytic activity under various laser irradiation wavelengths.Based on the confirmed biocompatibility,RhTeNRs were introduced into in vitro and in vivo cancer phototherapies.The results confirmed the selective physical death of cancer cells in the local area through laser irradiation.While chemotherapy does not guarantee successful treatment due to side effects and resistance,phototherapy using heat and reactive oxygen species generation of RhTeNRs induces physical death.
Avelino Dos Santos Da CostaRamesh SubbiahSeung Ja Oh
13页
查看更多>>摘要：The mechanism by which stromal cells fill voids in injured tissue remains a fundamental question in regenerative medicine.While it is well-established that fibroblasts fill voids by depositing extracellular matrix(ECM) proteins as they migrate toward the wound site,little is known about their ability to adopt an epithelial-like purse-string behavior.To investigate fibroblast behavior during gap closure,we created an artificial wound with a large void space.We discovered that fibroblasts could form a freestanding bridge over deep microvoids,closing the void via purse-string contraction,a mechanism previously thought to be unique to epithelial wound closure.The findings also revealed that myosin II mediated contractility and intercellular adherent junctions were required for the closure of the fibroblast gap in our fabricated three-dimensional artificial wound.To fulfill their repair function under the specific microenvironmental conditions of wounds,fibroblasts appeared to acquire the structural features of epithelial cells,namely,contractile actin bundles that span over multiple cells along the boundary.These findings shed light on a novel mechanism by which stromal cells bridge the 3D gap during physiological processes such as morphogenesis and wound healing.
查看更多>>摘要：Sonodynamic therapy(SDT),a noninvasive therapy that relies on sonosensitizers and generates reactive oxygen species(ROS),has attracted considerable attention in the treatment of pancreatic cancer.However,being surrounded by dense stromal barriers,pancreatic cancer exhibits high interstitial fluid pressure(IFP) and hypoxia in the tumor microenvironment(TME),resulting in poor SDT efficacy.Collagenase-loaded hollow TiO2(Col-H-TiO2) nanoparticles(NPs) capable of degrading stromal barriers and producing sufficient ROS production were synthesized in this study.After administration of NPs in the patient-derived xenograft(PDX) model,ultrasonic irradiation-released collagenase degraded tumor matrix fibers,decreased intratumoral IFP,and enhanced the penetration and retention of NPs within tumor tissues.Moreover,the NPs accumulated within the tumor not only generate abundant ROS under the influence of ultrasound irradiation but also improve intratumoral ultrasound signal,providing ultrasonic imaging-guided highly effective SDT for pancreatic cancer.In conclusion,this research improves the SDT technique and enhances the visualization of pancreatic cancer by remodeling the TME and is a promising strategy for further clinical applications.
查看更多>>摘要：Hypoxia-activated prodrugs(HAPs) have drawn increasing attention for improving the antitumor effects while minimizing side effects.However,the heterogeneous distribution of the hypoxic region in tumors severely impedes the curative effect of HAPs.Additionally,most HAPs are not amenable to optical imaging,and it is difficult to precisely trace them in tissues.Herein,we carefully designed and synthesized a multifunctional therapeutic BAC prodrug by connecting the chemotherapeutic drug camptothecin(CPT) and the fluorescent photothermal agent boron dipyrromethene(BODIPY) via hypoxia-responsive azobenzene linkers.To enhance the solubility and tumor accumulation,the prepared BAC was further encapsulated into a human serum albumin(HSA)-based drug delivery system to form HSA@BAC nanoparticles.Since the CPT was caged by a BODIPY-based molecule at the active site,the BAC exhibited excellent biosafety.Importantly,the activated CPT could be quickly released from BAC and could perform chemotherapy in hypoxic cancer cells,which was ascribed to the cleavage of the azobenzene linker by overexpressed azoreductase.After irradiation with a 730 nm laser,HSA@BAC can efficiently generate hyperthermia to achieve irreversible cancer cell death by oxygen-independent photothermal therapy.Under fluorescence imaging-guided local irradiation,both in vitro and in vivo studies demonstrated that HSA@BAC exhibited superior antitumor effects with minimal side effects.
查看更多>>摘要：Piezol is a recently discovered Ca~(2+) permeable ion channel that has emerged as an integral sensor of hemodynamic forces within the cardiovascular system,contributing to vascular development and blood pressure regulation.However,how the composition of the extracellular matrix(ECM) affects the mechanosensitivity of Piezol in response to hemodynamic forces remains poorly understood.Using a combination of microfluidics and calcium imaging techniques,we probe the shear stress sensitivity of single HEK293T cells engineered to stably express Piezol in the presence of different ECM proteins.Our experiments show that Piezol sensitivity to shear stress is not dependent on the presence of ECM proteins.However,different ECM proteins regulate the sensitivity of Piezol depending on the shear stress level.Under high shear stress,fibronectin sensitizes Piezol response to shear,while under low shear stress,Piezol mechanosensitivity is improved in the presence of collagen types I and IV and laminin.Moreover,we report that α5β1 and αvβ3 integrins are involved in Piezol sensitivity at high shear,while αvβ3 and αvβ5 integrins are involved in regulating the Piezol response at low shear stress.These results demonstrate that the ECM/integrin interactions influence Piezol mechanosensitivity and could represent a mechanism whereby extracellular forces are transmitted to Piezol channels,providing new insights into the mechanism by which Piezol senses shear stress.
查看更多>>摘要：Sucrose is one of the most applied carbon sources in the fermentation process,and it directly determines the microbial metabolism with its concentration fluctuation.Meanwhile,sucrose also plays a key role of a protective agent in the production of biological vaccines,especially in the new mRNA vaccines for curing COVID-19.However,rapid and precise detection of sucrose is always desired but unrealized in industrial fermentation and synthetic biology research.In order to address the above issue,we proposed an ultrasensitive biosensor microchip achieving accurate sucrose recognition within only 12 s,relying on the construction of a Prussian blue analogue@Au edge-rich(PBA@AuER) microarchitecture.This special geometric structure was formed through exactly inducing the oriented PBA crystallization toward a certain plane to create more regular and continuous edge features.This composite was further transformed to a screen-printed ink to directly and composite was further transformed to a screen-printed ink to directly and large-scale fabricate an enzymatic biosensor microchip showing ultrahigh sensitivity,a wide detection range,and a low detection limit to the accurate sucrose recognition.As confirmed in a real alcohol fermentation reaction,the as-prepared microchip enabled us to accurately detect the sucrose and glucose concentrations with outstanding reusability(more than 300 times) during the whole process through proposing a novel analytical strategy for the binary mixture substrate system.
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