Mild synthesis of ultra-bright carbon dots with solvatochromism for rapid lipid droplet monitoring in varied physiological processes.

Lipid droplets (LDs) participating in various cellular activities and are increasingly being emphasized. Fluorescence imaging provides powerful tool for dynamic tracking of LDs, however, most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield (PLQY), poor photostability and tedious washing procedures. Herein, a novel yellow-emissive carbon dot (OT-CD) has been synthesized conveniently with high PLQY up to 90%. Besides, OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2, which is much higher than most LDs probes. These characters enable OT-CD high brightness, stable and wash-free LDs probing, and feasible for in vivo imaging. Then, detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded, including ferroptosis and other diseases processes. Furthermore, fast whole imaging of zebrafish and identified LD enrichment in injured liver indicate its further feasibility for in vivo application. In contrast to the reported studies to date, this approach provides a versatile conventional synthesis system for high-performance LDs targeting probes, combing the advantages of easy and high-yield production, as well as robust brightness and stability for long-term imaging, facilitating investigations into organelle interactions and LD-associated diseases.

Bioactive cell niche mediating uniform thermal stimulus for BMSC neural differentiation through TRPV1 channel activation.

As one of the physical stimulus tools to target neuromodulation-related biological entities, mild thermal stimulus has attracted increasing attention in unraveling neural differentiation processing. However, thermal stimulus for neural behavior regulation has been relatively unexplored due to the challenge in finding a good method of exerting thermal stimulus. Considering the distance-dependent temperature preservation efficiency and the native importance of a bioactive matrix, we herein put forward the design of a photothermal hydrogel by immobilizing photothermal dopamine (DA) in hyaluronic acid (HA) chains. Benefitting from the minuscule disaccharide repeat unit size (≈1 nm) of HA used for the DA grafting, and the additional adhesion capacity of the DA for recruiting cells, a uniformly close distance from heating source to cells is realized. Therefore, we successfully established a near-infrared light initiated photothermal stimulus platform, with full bioactivity and high thermal manipulation efficiency. After extensive characterization, we proved that the thermal activation, from matrix to cells, triggered TRPV1 ion channel opening and Ca2+ influx, which finally promoted neural differentiation of bone marrow mesenchymal stem cells (BMSCs). This work broadens the possibilities of polymeric photothermal materials, and is of great significance for remotely manipulating neural and other cellular machinery for stem cell therapeutics in tissue engineering.

Orange-Emissive Carbon Dots with High Photostability for Mitochondrial Dynamics Tracking in Living Cells.

Mitochondria play significant roles in maintaining a stable internal environment for cell metabolism. Hence, real-time monitoring of the dynamics of mitochondria is essential for further understanding mitochondria-related diseases. Fluorescent probes provide powerful tools for visualizing dynamic processes. However, most mitochondria-targeted probes are derived from organic molecules with poor photostability, making long-term dynamic monitoring challenging. Herein, we design a novel mitochondria-targeted probe based on carbon dots with high performance for long-term tracking. Considering that the targeting ability of CDs is related to surface functional groups, which are generally determined by the reaction precursors, we successfully constructed mitochondria-targeted O-CDs with emission at 565 nm through solvothermal treatment of m-diethylaminophenol. The O-CDs are bright with a high quantum yield of 12.61%, high mitochondria-targeting ability, and good stability. The O-CDs possess a high quantum yield (12.61%), specific mitochondria-targeting ability, and outstanding optical stability. Owing to the abundant hydroxyl and ammonium cations on the surface, O-CDs showed obvious accumulation in mitochondria with a high colocalization coefficient of up to 0.90 and remained steady even after fixation. Besides, O-CDs showed outstanding compatibility and photostability under various interruptions or long-time irradiation. Therefore, O-CDs are preferable for the long-term tracking of dynamic mitochondrial behavior in live cells. We first observed the mitochondrial fission and fusion behaviors in HeLa cells, and then, the size, morphology, and distribution of mitochondria in physiological or pathological conditions were clearly recorded. More importantly, we observed different dynamics interactions between mitochondria and lipid droplets during the apoptosis and mitophagy processes. This study provides a potential tool for exploring interactions between mitochondria and other organelles, further promoting the research on mitochondria-related diseases.

Wireless-Powering Deep Brain Stimulation Platform Based on 1D-Structured Magnetoelectric Nanochains Applied in Antiepilepsy Treatment.

Electrical deep brain stimulation (DBS) is a top priority for pharmacoresistant epilepsy treatment, while less-invasive wireless DBS is an urgent priority but challenging. Herein, we developed a conceptual wireless DBS platform to realize local electric stimulation via 1D-structured magnetoelectric Fe3O4@BaTiO3 nanochains (FBC). The FBC was facilely synthesized via magnetic-assisted interface coassembly, possessing a higher electrical output by inducing larger local strain from the anisotropic structure and strain coherence. Subsequently, wireless magnetoelectric neuromodulation in vitro was synergistically achieved by voltage-gated ion channels and to a lesser extent, the mechanosensitive ion channels. Furthermore, FBC less-invasively injected into the anterior nucleus of the thalamus (ANT) obviously inhibited acute and continuous seizures under magnetic loading, exhibiting excellent therapeutic effects in suppressing both high voltage electroencephalogram signals propagation and behavioral seizure stage and neuroprotection of the hippocampus mediated via the Papez circuit similar to conventional wired-in DBS. This work establishes an advanced antiepilepsy strategy and provides a perspective for other neurological disorder treatment.

Magnetic manipulation of Fe3O4@BaTiO3 nanochains to regulate extracellular topographical and electrical cues.

Magnetic fields play an essential role in material science and biomedical engineering. Magnetic-responsive materials can be arranged orderly in matrix to realize the construction of an aligned scaffold under magnetic induction. However, a single topological cue is insufficient to activate neural tissue regeneration, demanding more cues to promote regeneration synergistically, such as electrical stimulation and a biomimetic matrix. Herein, we propose one-dimensional (1D) magnetoelectric Fe3O4@BaTiO3 nanochains with controllable lengths under the regulation of a magnetic field. These nanochains can be oriented in the biomimetic hydrogel under magnetic guidance and induce the hydrogel microfiber to align along the direction of the nanochains, which is beneficial for cell-oriented outgrowth. This aligned hydrogel enabled wireless electrical stimulation mediated by magnetoelectric nanochains under magnetic stimulation, thereby activating the voltage-gated ion channel. Consequently, topological and electrical cues in this multifunctional biomimetic hydrogel synergistically enhanced the expression of neural functional proteins, facilitating synapse remodeling and neural regeneration. Predictably, the construction of multifunctional hydrogels based on low-cost and facile synthesis of magnetoelectric nanochains is an emerging patient-friendly and effective therapeutic strategy for neural or other tissue regeneration. STATEMENT OF SIGNIFICANCE: A facile and controllable magnetic strategy is established to manipulate 1D nanomaterial growth, matrix topography, and wireless electrical stimulation of cells. First, the magnetic-assisted interface co-assembly was used to control the length of Fe3O4@BaTiO3 nanochains with enhanced magnetoelectric effect. Then, the motion of the magnetic-induced nanochains guided the orientation of nanofibers in a 3D biomimetic hydrogel matrix. Finally, wireless electrical signals and topological cues in the biomimetic matrix synergistically promoted orderly aligned cell outgrowth and membrane depolarization by Ca2+ influx, thus enhancing nerve cell synaptic plasticity and functional expression. Consequently, this work provides a conceptual strategy from material design to extracellular matrix signal manipulation and synergistic induction of tissue regeneration.

An upconversion nanoparticle-integrated fibrillar scaffold combined with a NIR-optogenetic strategy to regulate neural cell performance.

Optogenetics using light-sensitive proteins such as calcium transport channel rhodopsin (CatCh) opens up new possibilities for non-invasive remote manipulation of neural function. However, current optogenetic approaches for neurological disorder therapies rely on visible light excitation and are rarely applied to neurogenesis and nerve regeneration. Herein, we propose a new strategy for tissue engineering which combines optogenetic technology and biomimetic nerve scaffolds. Upconversion nanoparticles (UCNPs) were synthesized and integrated with oriented fibrillar PCL membranes with a collagen coating to establish neuro-matrix interfaces. Benefiting from the excellent bioactivity, oriented fibrillation and NIR-photoresponsivity, the CatCh-transfected PC12 cells on these interfaces exhibited enhanced cell elongation and neurite extension, as well as upregulated neurogenesis upon NIR excitation. Furthermore, a UCNP-integrated scaffold as an optogenetic actuator allowed NIR to penetrate dermal tissues to mediate neural activation, with an efficiency comparable to that of a 470 nm blue light. Compared with current visible light-excited optogenetics, our composite scaffold-mediated NIR stimulation addresses the problem of tissue penetration and will enable less-invasive neurofunctional manipulation, with the potential for remote therapy.

"Three-in-one" platform based on Fe-CDs nanozyme for dual-mode/dual-target detection and NIR-assisted bacterial killing.

As nanozymes, carbon dots (CDs) have attracted increasing attention due to their remarkable properties. Besides general enzyme activity, their photoluminescence and photothermal properties have been explored rarely, whereas their synergistic effects might produce CDs-based nanozymes of high performance. Here, iron-doped CDs (Fe-CDs) with tunable fluorescence and enhanced peroxidase-like activity were designed to develop a novel "three-in-one" multifunctional platform to provide dual-mode/dual-target detection and near infrared (NIR)-assisted antibacterial ability. This proposed strategy for a H2O2 test exhibited a wide linear relationship with a low limit of detection (LOD) of 0.16 µM (colorimetric) and 0.14 µM (ratiometric fluorescent). Furthermore, due to the nature of cholesterol being oxidized to H2O2 by cholesterol oxidase, sensitive and selective detection of cholesterol was realized, and the LOD was 0.42 µM (colorimetric) and 0.27 µM (ratiometric fluorescent), surpassing that reported previously. This result suggested that Fe-CDs could be used for dual-mode quantification of large family of H2O2-producing metabolites, thereby paving the way for developing multi-mode sensing strategies based on nanozymes. Moreover, this platform showed synergistic effects for antibacterial application, indicating great prospects for bacterial killing as well as wound disinfection and healing. Hence, this platform could contribute to the construction of multifunctional CDs with high performance.