Metabolites can directly reflect and modulate cell responses and phenotypical changes by influencing energy balances, intercellular signals, and many other cellular functions throughout the lifespan ...of cells. Taking into account the heterogeneity of cells, single-cell metabolite analysis offers an insight into the functional process within one cell. Microfluidics as a powerful tool has attracted significant interest in the single-cell metabolite analysis field. The microfluidic platform is possible to observe, classify, and stimulate individual cells. It can also transport single-cell to subsequent analysis steps in a fast and controllable way to determine and analyze the composition and content of metabolites. The reviews of topics in microfluidics for single-cell metabolite analysis have been published in the past few years. However, most of them focused on metabolite analysis with mass spectrometry. Here, we covered the advances of microfluidic devices for single-cell metabolite analysis, with a focus on single-cell isolation and manipulation. What is more, we summarized the detection methods and applications of single-cell metabolites.
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Vascular systems are responsible for various physiological and pathological processes related to all organs in vivo, and the survival of engineered tissues for enough nutrient supply in vitro. Thus, ...biomimetic vascularization is highly needed for constructing both a biomimetic organ model and a reliable engineered tissue. However, many challenges remain in constructing vascularized tissues, requiring the combination of suitable biomaterials and engineering techniques. In this review, the advantages of hydrogels on building engineered vascularized tissues are discussed and recent engineering techniques for building perfusable microchannels in hydrogels are summarized, including micromolding, 3D printing, and microfluidic spinning. Furthermore, the applications of these perfusable hydrogels in manufacturing organ‐on‐a‐chip devices and transplantable engineered tissues are highlighted. Finally, current challenges in recapitulating the complexity of native vascular systems are discussed and future development of vascularized tissues is prospected.
Complicated vascular systems play an important role in all organs and tissues. To recapitulate the blood vessel systems in hydrogels for building engineered tissues is still challenging. This review provides a summary of the state‐of‐the‐art engineering methods for fabricating vessel‐like‐microchannels in hydrogel materials and discusses their enormous potential in tissue transplantation and organ‐on‐a‐chip fields.
The development of high‐efficiency nanozymes is of great significance in the field of nanozymology, because this is one of the prerequisites for the sophisticated performance of nanozymes. Herein, ...the developed metal–ligand cross‐linking strategy engineers porous carbon nanorod supported ultra‐small iron carbide nanoparticles that possess excellent oxidase‐like and peroxidase‐like enzyme activities. The fabricated nanozyme can efficiently accelerate the oxidation of ascorbate (AA) to enhance cancer cells ablation efficacy. Due to the nanozyme having great surface atoms utilization ratio and large specific surface area, the AA can be rapidly and completely autoxidized within 20 min. Mechanism research demonstrates that the nanozyme's first activation of O2 to generate superoxide free radicals (O2•−) via the oxidase‐like pathway, then the O2•− directly oxidizes AA and produces hydrogen peroxide (H2O2). Simultaneously, the H2O2 transforms into the toxic hydroxyl radical through the peroxidase‐like pathway and induces tumor cell death. Further in vitro and in vivo assays show the significant enhancement of the anti‐tumor efficacy through AA oxidation which is catalyzed by the developed nanozyme. It is expected that this work will benefit not only the development of other efficient nanozymes, but also future advances in the field of AA oxidation induced tumor therapy.
Dual enzyme mimics engineered based on a metal–ligand cross‐linking strategy has excellent oxidase‐like and peroxidase‐like enzyme activities. It can efficiently accelerate the oxidation of ascorbate to produce toxic hydroxyl radical. Further in vitro and in vivo experiments show that the nanozyme can significantly enhance the anti‐tumor efficacy by catalyzing the oxidation of ascorbate.
Unprecedented advances in metal nanoparticle synthesis have paved the way for broad applications in sensing, imaging, catalysis, diagnosis, and therapy by tuning the optical properties, enhancing ...catalytic performance, and improving chemical and biological properties of metal nanoparticles. The central guiding concept for regulating the size and morphology of metal nanoparticles is identified as the precise manipulation of nucleation and subsequent growth, often known as seed‐mediated growth methods. However, since the growth process is sensitive not only to the metal seeds but also to capping agents, metal precursors, growth solution, growth/incubation time, reductants, and other influencing factors, the precise control of metal nanoparticle morphology is multifactorial. Further, multiple reaction parameters are entangled with each other, so it is necessary to clarify the mechanism by which each factor precisely regulates the morphology of metal nanoparticles. In this review, to exploit the generality and extendibility of metal nanoparticle synthesis, the mechanisms of growth influencing factors in seed‐mediated growth methods are systematically summarized. Second, a variety of critical properties and applications enabled by grown metal nanoparticles are focused upon. Finally, the current progress and offer insights on the challenges, opportunities, and future directions for the growth and applications of grown metal nanoparticles are reviewed.
The state‐of‐the‐art development in seeded growth methods from key influencing factors of growth and applications of grown metal nanoparticles are summarized in this review to highlight the achievements and help researchers understand the current investigation status of seed‐mediated methods. Furthermore, the challenges faced by seed‐mediated methods are outlined and the future directions for advancing seed‐mediated methods are outlooked.
Nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) is crucial for oxidation-reduction equilibrium in all living cells, and disturbance of NAD(P)H/NAD(P)+ indicates many diseases. To ...accurately detect and track NAD(P)H in vitro and in vivo, we have developed a small organic dye (Rh-QL) based on intramolecular charge transfer (ICT) mechanism for multimodally detecting NAD(P)H by visible and near-infrared (Vis-NIR) dual-channel lighting-up fluorescence and by near-infrared spectrophotometry. This quinoline-based Indicator showed high selectivity and sensitivity toward NAD(P)H with a large redshift of absorption and dual-channel emissions at 580 nm and 750 nm, spatiotemporally and synchronously. For liquid samples, Rh-QL succeeded to screen NAD(P)H-related G6PD enzymatic activity by responsive absorption at 710 nm. In living cells, Rh-QL exhibited a good bio-compatibility and remarkable mitochondrial-targeted capacity to visualize intracellular endogenous and exogenous NAD(P)H variation utilizing Vis-NIR dual-channel fluorescence. In vivo, the near-infrared fluorescence was applied to differentiate tumor-bearing mice by NAD(P)H imaging. Moreover, “glycolysis” in both cancer cells and tumors of mice were traced to produce extra NAD(P)H using Rh-QL. As the first Vis-NIR dual-channel lighting-up probe to multimodally detect and track NAD(P)H in vitro and in vivo, it is appealing for high efficiency in understanding NAD(P)H-related physiological and pathological processes of disease diagnosis and therapy.
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•A visible and near-infrared dual-emitting fluorescence probe (Rh-QL) was developed to multimodally detect NAD(P)H.•Fluorescence emitted at 580 nm and 750 nm, spatiotemporally and synchronously, with high selectivity, sensitivity.•G6PD enzymatic activity was screened successfully by the responsive absorption at 710 nm.•Rh-QL succeeded to visualize intracellular NAD(P)H variation with bio-compatibility and mitochondrial targeted capacity.•Rh-QL was successfully applied to differentiate tumor-bearing mice and traced NAD(P)H level by NAD(P)H imaging in vivo.
The vigorous nanomedicine offers significant possibilities for effective therapeutics of various diseases, and nanovesicles (NVs) represented by artificial liposomes and natural exosomes and ...cytomembranes especially show great potential. However, their complex interactions with cells, particularly the heterogeneous extracellular adsorptions, are difficult to analyze spatiotemporally due to the transient dynamics. In this study, by single NVs tracking, the extracellular NVs adsorptions are directly observed and their heterogeneous characteristics are revealed. Briefly, plenty of NVs adsorbed on HCT116 cells are tracked and classified, and it is discovered that they exhibit various diffusion properties from different extracellular regions: stable adsorptions on the rear surface and restricted adsorptions on the front protrusion. After the hydrolysis of hyaluronic acid in the extracellular matrix by hyaluronidase, the restricted adsorptions are further weakened and manifested as dissociative adsorptions, which demonstrated reduced total NVs adsorptions from a single-cell and single-particle perspective. Compared with traditional static analysis, the spatiotemporal tracking and heterogeneous results not only reveal the extracellular NVs-cell interactions but also inspire a wide variety of nanomedicine and their nano-investigations.
A novel probe was synthesized with a turn-on NIR fluorescent (NIRF)/photoacoustic (PA) response to NADPH, which was successfully applied in both monitoring intracellular NADPH and dual-modal imaging ...of tumor-bearing mice. It exhibits good potential in studying and understanding the tumor energy metabolism and treatment process related to NADPH.
Theranostics, integrating diagnostic and therapeutic functionalities, have emerged as advanced systems for timely cancer diagnosis and effective treatment. The development of versatile materials ...suitable for cancer theranostics is intensifying. Porphyrin-based metal-organic frameworks (MOFs) leverage the structural diversity and designability inherent in MOFs, alongside the robust photophysical, catalytic, and biological properties of porphyrins. These materials enhance the solubility and stability of porphyrins and facilitate their stable functionalized assemblies, conferring the potential for multimodal imaging diagnostics and precision therapeutics. In this review, we summarized the potential of porphyrin-based MOFs as cancer theranostics platforms, focusing on recent advancements in porphyrin-based MOFs, and highlighting their functionalized strategies and developments in diagnostic imaging and synergistic therapies. Finally, we proposed the challenges and prospects of these emerging materials in cancer theranostics.
•The advantages of porphyrin-based MOFs in cancer theranostics briefly outlined.•Multifunctional construction strategies of porphyrin-based MOFs for theranostics were summarized.•Various diagnostic imaging strategies involving porphyrin-based MOFs were discussed.•Various therapeutic strategies for cancer using porphyrin-based MOFs were detailed in-depth.
Noble metals and their alloy‐based nanomaterials are widely used in biomedicine, especially in the fields of photodynamic therapy (PDT) and photothermal therapy (PTT) on tumors, due to their ...remarkable physicochemical properties. Nonetheless, novel doping strategies with unexpected efficacies are still challenging and formidable. Herein, a photosensitizer‐alloy nanosystem is designed for highly efficient PDT and PTT. Specifically, the optimized Pt/Ag alloy nanoparticles are facilely synthesized in one step at room temperature and are simultaneously endowed with enhanced peroxidase‐like activity and photothermal conversion, and further activated cytotoxic singlet oxygen (1O2) productivity after covalent functionalization of chlorin e6 (Ce6). A small amount of Ag doping can kill two birds with one stone by simultaneously enhancing the synergistic PDT and PTT potential of Pt/Ag‐PEG‐Ce6 nanoparticles. Both in vitro and in vivo experimental results indicate that the significant temperature increase triggered by 808 nm laser and a large amount of toxic 1O2 excited by 671 nm laser synergistically and strongly kill tumor cells. Therefore, through proper doping and improved physicochemical properties, this nanosystem achieves effective PDT and PTT of tumors and also inspires the advanced design of noble metal‐based nanomedicine.
A novel photosensitizer‐alloy nanotherapeutic reagent for efficient photodynamic therapy (PDT) and photothermal therapy (PTT), Pt/Ag‐PEG‐Ce6, has been successfully fabricated and is applied to effectively kill tumor cells in vivo and in vitro, not only remarkably improving the PDT and PTT therapeutic effects, but also broadening the biomedical applications of noble metal‐based nanosystems and their alloy.
Air pollution is a serious threat to human health. Inhaled fine particulate matter (PM2.5) can cause inflammation and oxidative stress in the airway; however, the mechanisms responsible for this ...effect have yet to be elucidated and there are no specific drugs that can prevent and treat this condition. In the present study, we investigated the effects and mechanisms underlying the inhalation of salvianolic acid B (SalB) on PM2.5-induced airway inflammation and oxidative stress. We used a PM2.5-induced mouse model of airway inflammation and oxidative stress, along with a human epithelial cell model, to study the action and mechanisms of SalB by histopathology, real-time PCR, enzyme-linked immunosorbent assays, flow cytometry, and western blotting. SalB treatment markedly inhibited the PM2.5-induced increase in the number of neutrophils and macrophages in bronchoalveolar lavage fluid, improved the infiltration of inflammatory cells in lung tissue, and reduced injury in the alveolar septum. Furthermore, SalB reduced the mRNA and protein levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, keratinocyte (KC), and transforming growth factor- (TGF-) β1 in lung tissues and the protein levels of IL-1β, TNF-α, IL-8, IL-6, and TGF-β1 in human epithelial cells. SalB treatment also significantly prevented the reduction of levels of superoxide dismutase, catalase, glutathione, and glutathione peroxidase in lung tissue and reduced the levels of reactive oxygen species in human epithelial cells induced by PM2.5. Furthermore, SalB and the myeloid differentiation primary response 88 (MyD88) inhibitor ST2825 inhibited the expression levels of toll-like receptor 4 (TLR4), MyD88, tumor necrosis factor receptor associated factor 6 (TRAF-6), and NOD-like receptor protein 3 (NLRP3), as well as the phosphorylation of downstream Erk1/2 and P38 in lung tissue and epithelial cells. SalB protects against PM2.5-induced airway inflammation and oxidative stress in a manner that is associated with the inhibition of the TLR4/MyD88/TRAF-6/NLRP3 pathway and downstream signals ERK1/2 and P38.
