Activated alkyne-enabled turn-on click bioconjugation with cascade signal amplification for ultrafast and high-throughput antibiotic screening.

Antimicrobial susceptibility testing plays a pivotal role in the discovery of new antibiotics. However, the development of simple, sensitive, and rapid assessment approaches remains challenging. Herein, we report an activated alkyne-based cascade signal amplification strategy for ultrafast and high-throughput antibiotic screening. First of all, a novel water-soluble aggregation-induced emission (AIE) luminogen is synthesized, which contains an activated alkyne group to enable fluorescence turn-on and metal-free click bioconjugation under physiological conditions. Taking advantage of the in-house established method for bacterial lysis, a number of clickable biological substances (i.e., bacterial solutes and debris) are released from the bacterial bodies, which remarkably increases the quantity of analytes. By means of the activated alkyne-mediated turn-on click bioconjugation, the system fluorescence signal is significantly amplified due to the increased labeling sites as well as the AIE effect. Such a cascade signal amplification strategy efficiently improves the detection sensitivity and thus enables ultrafast antimicrobial susceptibility assessment. By integration with a microplate reader, this approach is further applied to high-throughput antibiotic screening.

Ultrasensitive Ratiometric Fluorescent Nanothermometer with Reverse Signal Changes for Intracellular Temperature Mapping.

Sensing temperature at the subcellular level is pivotal for gaining essential thermal insights into diverse biological processes. However, achieving sensitive and accurate sensing of the intracellular temperature remains a challenge. Herein, we develop a ratiometric organic fluorescent nanothermometer with reverse signal changes for the ultrasensitive mapping of intracellular temperature. The nanothermometer is fabricated from a binary mixture of saturated fatty acids with a noneutectic composition, a red-emissive aggregation-caused quenching luminogen, and a green-emissive aggregation-induced emission luminogen using a modified nanoprecipitation method. Different from the eutectic mixture with a single phase-transition point, the noneutectic mixture possesses two solid-liquid phase transitions, which not only allows for reversible regulation of the aggregation states of the encapsulated luminogens but also effectively broadens the temperature sensing range (25-48 °C) across the physiological temperature range. Remarkably, the nanothermometer exhibits reverse and sensitive signal changes, demonstrating maximum relative thermal sensitivities of up to 63.66% °C-1 in aqueous systems and 44.01% °C-1 in the intracellular environment, respectively. Taking advantage of these outstanding thermometric performances, the nanothermometer is further employed to intracellularly monitor minute temperature variations upon chemical stimulation. This study provides a powerful tool for the exploration of dynamic cellular thermal activities, holding great promise in unveiling intricate physiological processes.

Mechanically and Thermally Stable Cathode Electrolyte Interphase Enables High-temperature, High-voltage Li||LiCoO2 Batteries.

The development of high-energy-density Li||LiCoO2 batteries is severely limited by the instability of cathode electrolyte interphase (CEI) at high voltage and high temperature. Here we propose a mechanically and thermally stable CEI by electrolyte designing for achieving the exceptional performance of Li||LiCoO2 batteries at 4.6 V and 70 °C. 2,4,6-tris(3,4,5-trifluorophenyl)boroxin (TTFPB) as the additive could preferentially enter into the first shell structure of PF6 - solvation and be decomposed on LiCoO2 surface at low oxidation potential to generate a LiBx Oy -rich/LiF-rich CEI. The LiBx Oy surface layer effectively maintained the integrity of CEI and provided excellent mechanical and thermal stability while abundant LiF in CEI further improved the thermal stability and homogeneity of CEI. Such CEI drastically alleviated the crack and regeneration of CEI and irreversible phase transformation of the cathode. As expected, the Li||LiCoO2 batteries with the tailored CEI achieved 91.9 % and 74.0 % capacity retention after 200 and 150 cycles at 4.6 and 4.7 V, respectively. Moreover, such batteries also delivered an unprecedented high-temperature performance with 73.6 % capacity retention after 100 cycles at 70 °C and 4.6 V.

Bringing Inherent Charges into Aggregation-Induced Emission Research.

Charged organic molecules, such as DNA, RNA, proteins, and polysaccharides, are ubiquitous and indispensable in natural living systems, which possess specific biological functions to interact with oppositely charged species via electrostatic attraction. The molecules with inherent charges typically differentiate themselves from the neutral ones with unique attributes (e.g., ionic interactions and high polarity), thereby playing a pivotal role in a broad spectrum of areas, including supramolecular chemistry, structural biology, and materials science. It is thus of great importance to explore and develop various charged organic systems for biomimicry and the creation of functional materials. In 2001, our group reported a peculiar luminogen that exhibited weak emission in solution but had significantly enhanced emission in aggregates, and we, for the first time, coined this phenomenon as aggregation-induced emission (AIE). The AIE concept significantly changes the cognition of the scientific community toward classic photophysical phenomena. Since the discovery of this unusual luminescence phenomenon, AIE luminogens (AIEgens) have attracted extensive attention from researchers in a plethora of disciplines because of their high brightness in aggregates, large Stokes shift, excellent photostability, and good biocompatibility. In the past 10 years, our laboratory has expended a great amount of effort to bring inherent charges into AIE research and acquired fruitful achievements.In this Account, we summarize the progress of charged AIE systems primarily made by our laboratory. We start with a brief introduction to charged AIEgens and then discuss their design strategies from molecular and topological perspectives, respectively. Next, we review the unique properties of charged AIEgens, including D-A interactions, anion-π+ interactions, and intermolecular electrostatic interactions, with an emphasis on how they differentiate themselves from the neutral analogs. On the one hand, positively charged AIEgens exhibit unique photophysical properties by forming typical donor-acceptor structures to manipulate the emission wavelength or initiate ultralong persistent luminescence. On the other hand, positively charged AIEgens exhibit unique physiochemical properties, such as an adjustable targeting capability toward biological targets and a strong capability for the generation of reactive oxygen species. Furthermore, we showcase the applications of charged AIEgens in imaging and diagnosis, photodynamic therapy, gas separation, and solar desalination. Finally, we conclude this Account with a summary and some perspectives regarding the existing challenges and future directions. We hope that this Account can spark new ideas and inspire scientists from different disciplines to explore this nascent yet promising research area.

Reconstituting Low-Density Lipoprotein with NIR-Absorbing Organic Photothermal Agents for Targeted Killing of Cancer Cells.

Photothermal therapy (PTT) systems typically do not possess intrinsic tumor-targeting capability, resulting in indiscriminate thermal damage to both cancer and normal cells. Herein, a low-density lipoprotein (LDL)-based nanosystem (denoted as MTTQ@LDL) is reported for targeted photothermal killing of cancer cells. Such a nanosystem is fabricated by reconstituting the lipophilic core of LDL with an organic photothermal agent MTTQ. The reconstitution process improves the supramolecular photothermal effects of MTTQ assemblies, which contributes to the significantly enhanced photothermal conversion efficiency (41.3% vs. 16.2%). MTTQ@LDL can actively target LDL receptor-overexpressed cancer cells via receptor-mediated endocytosis, enabling the selective killing of cancer cells over normal cells (98% vs. 7%) post-NIR irradiation. Reconstituted LDL can serve as a promising platform for targeted delivery of functional materials, holding great promise in tumor eradication in vivo.

Armor-like Inorganic-rich Cathode Electrolyte Interphase Enabled by the Pentafluorophenylboronic Acid Additive for High-voltage Li||NCM622 Batteries.

Lithium metal batteries (LMBs) comprising Li metal anode and high-voltage nickel-rich cathode could potentially realize high capacity and power density. However, suitable electrolytes to tolerate the oxidation on the cathode at high cut-off voltage are urgently needed. Herein, we present an armor-like inorganic-rich cathode electrolyte interphase (CEI) strategy for exploring oxidation-resistant electrolytes for sustaining 4.8 V Li||LiNi0.6 Co0.2 Mn0.2 O2 (NCM622) batteries with pentafluorophenylboronic acid (PFPBA) as the additive. In such CEI, the armored lithium borate surrounded by CEI up-layer represses the dissolution of inner CEI moieties and also improves the Li+ conductivity of CEI while abundant LiF is distributed over whole CEI to enhance the mechanical stability and Li+ conductivity compared with polymer moieties. With such robust Li+ conductive CEI, the Li||NCM622 battery delivered excellent stability at 4.6 V cut-off voltage with 91.2 % capacity retention after 400 cycles. The excellent cycling performance was also obtained even at 4.8 V cut-off voltage.

Polarity-Sensitive Fluorescent Probe for Reflecting the Packing Degree of Bacterial Membrane Lipids.

The maintenance of an intact membrane structure is of great importance for bacteria to execute various biological functions. However, chemical probes for monitoring the dynamic changes of bacterial membranes are barely reported. Herein, we, for the first time, report a novel polarity-sensitive probe for reflecting the packing degree of bacterial membrane lipids. Specifically, we synthesize a membrane-targeting fluorescent probe (TICT-lipid) that possesses both twist intramolecular charge transfer and aggregation-induced emission properties. TICT-lipid exhibits sensitive responses to the minute difference in the packing degree of membrane lipids, facilitating rapid differentiation of Gram-negative and Gram-positive bacteria. Interestingly, in the presence of membrane-disrupting antibiotics, the localization of TICT-lipid shifts from the outer membrane to the cell membrane by outputting blue-shifted and enhanced emission, making the mechanism of action of antibiotics clearly visible. TICT-lipid is a polarity-sensitive fluorescent probe, holding great promise in the study of membrane-related bacterial processes and antibiotic screening.

Engineering of Portable Smartphone Integrated with Liposome-Encapsulated Curcumin for Onsite Visual Ratiometric Fluorescence Imaging of Hypochlorite.

Precisely onsite monitoring of hypochlorite (ClO- ) is of great significance to guide its rational use, reducing/avoiding its potential threat toward food safety and human health. Considering ClO- could quench fluorescence of curcumin (CCM) by oxidizing the o-methoxyphenol of CCM into benzoquinone, a portable ratiometric fluorescence sensor integrated with smartphone was designed for realizing the visual point-of-care testing (POCT) of ClO- . The amphiphilic phospholipid polymer was used as carrier to wrap curcumin, forming a novel liposome-encapsulated CCM, which provided a scaffold to bind with [Ru(bpy)3 ]2+ through electrostatic interaction, thus assembling [Ru(bpy)3 ]2+ -functionalized liposome-encapsulated CCM ([Ru(bpy)3 ]2+ @CCM-NPs). Further integrated with smartphone, visual imaging of [Ru(bpy)3 ]2+ @CCM-NPs could be achieved and the accurate onsite detection of ClO- could be realized with a detection limit of 66.31 nM and a linear range of 0.2210 to 80.0 µM. In addition, the sensor could monitor ClO- in real samples with an onsite detection time of ∼154.0 s.

Formation of NaF-Rich Solid Electrolyte Interphase on Na Anode through Additive-Induced Anion-Enriched Structure of Na+ Solvation.

High-capacity sodium (Na) anodes suffer from dendrite growth due to the high reactivity, which can be overcome through inducing a stable NaF-rich solid electrolyte interphase (SEI). Herein, we propose an additive strategy for realizing the anion-enriched structure of Na+ solvation to obtain a NaF-rich SEI. The electron-withdrawing acetyl group in 4-acetylpyridine (4-APD) increases the coordination number of PF6 - in the Na+ solvation sheath to facilitate PF6 - to decompose into NaF. Thus, the NaF-rich SEI with high mechanical stability and interfacial energy is formed to repress the growth of Na dendrites. With the 4-APD-contained electrolyte, the symmetric Na||Na cells show excellent cycling performance over 360 h at 1.0 mA cm-2 . Meanwhile, excellent stability is also achieved for Na||Na3 V2 (PO4 )2 O2 F full cells with high Coulombic efficiency (97 %) and capacity retention (91 %) after 200 cycles.

Highly Oxidation-Resistant Electrolyte for 4.7†V Sodium Metal Batteries Enabled by Anion/Cation Solvation Engineering.

Sodium metal batteries (SMBs) are considered as promising battery system due to abundant Na sources. However, poor compatibility between electrolyte and cathode severely impedes its development. Herein, we proposed an anion/cation solvation strategy for realizing 4.7 V resistant SMBs electrolyte with NaClO4 and trimethoxy(pentafluorophenyl)silane (TPFS) as dual additives (DA). The ClO4 - can rapidly transfer to the cathode surface and strongly coordinate with Na+ to form stable polymer-like chains with solvents. Meanwhile, TPFS can preferentially enter into the PF6 - anion solvation sheath for reducing PF6 -solvent interaction and effectively scavenge adverse electrolyte species for protecting electrode electrolyte interphases. Thus, such electrolyte elevates the oxidative stability of carbonate electrolytes from 3.77 to 4.75 V, and enables Na||Na3 V2 (PO4 )2 O2 F (NVPF) battery with a capacity retention of 93 % and an average Coulombic efficiency (CE) of 99.6 % after 500 cycles at 4.7 V.

A Sensitive and Reliable Organic Fluorescent Nanothermometer for Noninvasive Temperature Sensing.

Sensing temperature at the subcellular level is of great importance for the understanding of miscellaneous biological processes. However, the development of sensitive and reliable organic fluorescent nanothermometers remains challenging. In this study, we report the fabrication of a novel organic fluorescent nanothermometer and study its application in temperature sensing. First of all, we synthesize a dual-responsive organic luminogen that can respond to the molecular state of aggregation and environmental polarity. Next, natural saturated fatty acids with sharp melting points as well as reversible and rapid phase transition are employed as the encapsulation matrix to correlate external heat information with the fluorescence properties of the luminogen. To apply the composite materials for biological application, we formulate them into colloidally dispersed nanoparticles by a technique that combines in situ surface polymerization and nanoprecipitation. As anticipated, the resultant zwitterionic nanothermometer exhibits sensitive, reversible, reliable, and multiparametric responses to temperature variation within a narrow range around the physiological temperature (i.e., 37 °C). Taking spectral position, fluorescence intensity, and fluorescence lifetime as the correlation parameters, the maximum relative thermal sensitivities are determined to be 2.15% °C-1, 17.06% °C-1, and 17.72% °C-1, respectively, which are much higher than most fluorescent nanothermometers. Furthermore, we achieve the multimodal temperature sensing of bacterial biofilms using these three complementary fluorescence parameters. Besides, we also fabricate a cationic form of the nanothermometer to facilitate efficient cellular uptake, holding great promise for studying thermal behaviors in biological systems.

Roles of VE-Cadherin in Hypoxia Induced Injury of Pulmonary Microvascular Endothelial Barrier.

BACKGROUND: Hypoxia induced injury of pulmonary microvascular endothelial barrier is closely related to the pathogenesis of acute lung injury after lung transplantation. VE-cadherin is an important structural molecule for pulmonary microvascular endothelial barrier. In this study, we aim to investigate the roles of VE-cadherin in hypoxia induced injury of pulmonary microvascular endothelial barrier. METHODS: Rat model of hypoxia and cultured pulmonary microvascular endothelial cells (PMVECs) were utilized. Determination of PMVECs apoptosis, skeleton combination was conducted to verify the effects of hypoxia on injury of pulmonary microvascular endothelial barrier. In addition, VE-cadherin expression was modulated by administration of siRNA in order to investigate the roles of VE-cadherin in hypoxia induced PMVECs apoptosis and skeleton recombination. RESULTS: Our data indicated that expression of VE-cadherin was down-regulated in hypoxia-exposed PMVECs. Whereas, in the cells treated using siRNA, down-regulation of VE-cadherin did not trigger PMVECs apoptosis, but it increased the sensitivity of PMVECs to the hypoxia induced apoptosis. In cases of hypoxia, the expression of VE-cadherin was significantly down-regulated, together with endothelial skeleton recombination and increase of permeability, which then triggered endothelial barrier dysfunction. CONCLUSIONS: These data verify that VE-cadherin expression played an important role in hypoxia induced PMVECs apoptosis and cellular skeletal recombination.

Heteroaromatic Hyperbranched Polyelectrolytes: Multicomponent Polyannulation and Photodynamic Biopatterning.

We reported an efficient multicomponent polyannulation for in situ generation of heteroaromatic hyperbranched polyelectrolytes by using readily accessible internal diynes and low-cost, commercially available arylnitriles, NaSbF6 , and H2 O/AcOH. The polymers were obtained in excellent yields (up to 99 %) with extraordinary high molecular weights (Mw up to 1.011×106 ) and low polydispersity indices. The resulting polymers showed good processibility and high quantum yields with tunable emission in the solid state, making them ideal materials for highly ordered fluorescent photopatterning. These hyperbranched polyelectrolytes also possessed strong ability to generate reactive oxygen species, which allowed their applications in efficient bacterial killing and customizable photodynamic patterning of living organisms in a simple and cost-effective way.

Promoting the Outgrowth of Neurites on Electrospun Microfibers by Functionalization with Electrosprayed Microparticles of Fatty Acids.

Controlling the outgrowth of neurites is important for enhancing the repair of injured nerves and understanding the development of nervous systems. Herein we report a simple strategy for enhancing the outgrowth of neurites through a unique integration of topographical guidance and a chemical cue. We use electrospray to easily functionalize the surface of a substrate with microparticles of natural fatty acids at a controllable density. Through a synergistic effect from the surface roughness arising from the microparticles and the chemical cue offered by the fatty acids, the outgrowth of neurites from PC12 cells is greatly enhanced. We also functionalize the surfaces of uniaxially aligned, electrospun microfibers with the microparticles and further demonstrate that the substrates can guide and enhance directional outgrowth of neurites from both PC12 multicellular spheroids and chick embryonic dorsal root ganglia bodies.

Integration of Phase-Change Materials with Electrospun Fibers for Promoting Neurite Outgrowth under Controlled Release.

We report a temperature-regulated system for the controlled release of nerve growth factor (NGF) to promote neurite outgrowth. The system is based upon microparticles fabricated using coaxial electrospray, with the outer solution containing a phase-change material (PCM) and the inner solution encompassing payload(s). When the temperature is kept below the melting point of the PCM, there is no release due to the extremely slow diffusion through a solid matrix. Upon increasing the temperature to slightly pass the melting point, the encapsulated payload(s) can be readily released from the melted PCM. By leveraging the reversibility of the phase transition, the payload(s) can be released in a pulsatile mode through on/off heating cycles. The controlled release system is evaluated for potential use in neural tissue engineering by sandwiching the microparticles, co-loaded with NGF and a near-infrared dye, between two layers of electrospun fibers to form a tri-layer construct. Upon photothermal heating with a near-infrared laser, the NGF is released with well-preserved bioactivity to promote neurite outgrowth. By choosing different combinations of PCM, biological effector, and scaffolding material, this controlled release system can be applied to a wide variety of biomedical applications.

Biomimetics: reconstitution of low-density lipoprotein for targeted drug delivery and related theranostic applications.

Low-density lipoprotein (LDL), one of the four major groups of lipoproteins for lipid transport in vivo, is emerging as an attractive carrier for the targeted delivery of theranostic agents. In contrast to the synthetic systems, LDL particles are intrinsically biocompatible and biodegradable, together with reduced immunogenicity and natural capabilities to target cancerous cells and to escape from the recognition and elimination by the reticuloendothelial system. Enticed by these attributes, a number of strategies have been developed for reconstituting LDL particles, including conjugation to the apolipoprotein, insertion into the phospholipid layer, and loading into the core. Here we present a tutorial review on the development of reconstituted LDL (rLDL) particles for theranostic applications. We start with a brief introduction to LDL and LDL receptor, as well as the advantages of using rLDL particles as a natural and versatile platform for the targeted delivery of theranostic agents. After a discussion of commonly used strategies for the reconstitution of LDL, we highlight the applications of rLDL particles in the staging of disease progression, treatment of lesioned tissues, and delivery of photosensitizers for photodynamic cancer therapy. We finish this review with a perspective on the remaining challenges and future directions.

Enhancing the Mechanical Properties of Electrospun Nanofiber Mats through Controllable Welding at the Cross Points.

This communication describes a simple and effective method for welding electrospun nanofibers at the cross points to enhance the mechanical properties of their nonwoven mats. The welding is achieved by placing a nonwoven mat of the nanofibers in a capped vial with the vapor of a proper solvent. For polycaprolactone (PCL) nanofibers, the solvent is dichloromethane (DCM). The welding can be managed in a controllable fashion by simply varying the partial pressure of DCM and/or the exposure time. Relative to the pristine nanofiber mat, the mechanical strength of the welded PCL nanofiber mat can be increased by as much as 200%. Meanwhile, such a treatment does not cause any major structural changes, including morphology, fiber diameter, and pore size. This study provides a generic method for improving the mechanical properties of nonwoven nanofiber mats, holding great potential in various applications.

Reconstitution of Low-Density Lipoproteins with Fatty Acids for the Targeted Delivery of Drugs into Cancer Cells.

Low-density lipoproteins (LDLs) are a class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. A facile procedure is used for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts. According to a hypothesized mechanism, the reconstituted LDLs can also enable metabolism-triggered drug release while preventing the payloads from lysosomal degradation. This study demonstrates that LDLs reconstructed with fatty acids hold great promise to serve as effective and versatile nanocarriers for targeted cancer therapy.

A Hybrid Nanomaterial for the Controlled Generation of Free Radicals and Oxidative Destruction of Hypoxic Cancer Cells.

Anticancer modalities based on oxygen free radicals, including photodynamic therapy and radiotherapy, have emerged as promising treatments in the clinic. However, the hypoxic environment in tumor tissue prevents the formation of oxygen free radicals. Here we introduce a novel strategy that employs oxygen-independent free radicals generated from a polymerization initiator for eradicating cancer cells. The initiator is mixed with a phase-change material and loaded into the cavities of gold nanocages. Upon irradiation by a near-infrared laser, the phase-change material is melted due to the photothermal effect of gold nanocages, leading to the release and decomposition of the loaded initiator to generate free radicals. The free radicals produced in this way are highly effective in inducing apoptosis in hypoxic cancer cells.

Micropatterning of the Ferroelectric Phase in a Poly(vinylidene difluoride) Film by Plasmonic Heating with Gold Nanocages.

Polymer thin films with patterned ferroelectric domains are attractive for a broad range of applications, including the fabrication of tactile sensors, infrared detectors, and non-volatile memories. Herein, we report the use of gold nanocages (AuNCs) as plasmonic nanostructures to induce a ferroelectric-paraelectric phase transition in a poly(vinylidene fluoride) (PVDF) thin film by leveraging its photothermal effect. This technique allows us to generate patterned domains of ferroelectric PVDF within just a few seconds. The incorporation of AuNCs significantly enhances the pyroelectric response of the ferroelectric film under near-infrared irradiation. We also demonstrate the use of such patterned ferroelectric films for near-infrared sensing/imaging.