Single-Step Low-Temperature Synthesis of Carbon Dots for Advanced Multiparametric Bioimaging Probe Applications.

Carbon dots (CDs) have recently emerged in biomedical and agricultural domains, mainly for their probe applications in developing efficient sensors. However, the existing high-temperature approaches limit the industrial level scaling up to further translate them into different products by mass-scale fabrication of CDs. To address this, we have attempted to lower the synthesis temperature to 140 °C and synthesized different CDs using different organic acids and their combinations in a one-step approach (quantum yield 3.6% to 16.5%; average size 3 to 5 nm). Further, sensing applications of CDs have been explored in three different biological models, mainly Danio rerio (zebrafish) embryos, bacterial strains, and the Lactuca sativa (lettuce) plant. The 72 h exposure of D. rerio embryos to 0.5 and 1 mg/mL concentrations of CDs exhibited significant uptake without mortality, a 100% hatching rate, and nonsignificant alterations in heart rate. Bacterial bioimaging experiments revealed CD compatibility with Gram-positive (Bacillus subtilis) and Gram-negative (Serratia marcescens) strains without bactericidal effects. Furthermore, CDs demonstrated effective conduction and fluorescence within the vascular system of lettuce plants, indicating their potential as in vivo probes for plant tissues. The single-step low-temperature CD synthesis approach with efficient structural and optical properties enables the process as industrially viable to up-scale the technology readiness level. The bioimaging of CDs in different biological models indicates the possibility of developing a CD probe for diverse biosensing roles in diseases, metabolism, microbial contamination sensing, and more.

Progress in the development of piezoelectric biomaterials for tissue remodeling.

Piezoelectric biomaterials have demonstrated significant potential in the past few decades to heal damaged tissue and restore cellular functionalities. Herein, we discuss the role of bioelectricity in tissue remodeling and explore ways to mimic such tissue-like properties in synthetic biomaterials. In the past decade, biomedical engineers have adopted emerging functional biomaterials-based tissue engineering approaches using innovative bioelectronic stimulation protocols based on dynamic stimuli to direct cellular activation, proliferation, and differentiation on engineered biomaterial constructs. The primary focus of this review is to discuss the concepts of piezoelectric energy harvesting, piezoelectric materials, and their application in soft (skin and neural) and hard (dental and bone) tissue regeneration. While discussing the prospective applications as an engineered tissue, an important distinction has been made between piezoceramics, piezopolymers, and their composites. The superiority of piezopolymers over piezoceramics to circumvent issues such as stiffness mismatch, biocompatibility, and biodegradability are highlighted. We aim to provide a comprehensive review of the field and identify opportunities for the future to develop clinically relevant and state-of-the-art biomaterials for personalized and remote health care.

Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases.

3D-Printed Materials for Wastewater Treatment.

The increasing levels of water pollution pose an imminent threat to human health and the environment. Current modalities of wastewater treatment necessitate expensive instrumentation and generate large amounts of waste, thus failing to provide ecofriendly and sustainable solutions for water purification. Over the years, novel additive manufacturing technology, also known as three-dimensional (3D) printing, has propelled remarkable innovation in different disciplines owing to its capability to fabricate customized geometric objects rapidly and cost-effectively with minimal byproducts and hence undoubtedly emerged as a promising alternative for wastewater treatment. Especially in membrane technology, 3D printing enables the designing of ultrathin membranes and membrane modules layer-by-layer with different morphologies, complex hierarchical structures, and a wide variety of materials otherwise unmet using conventional fabrication strategies. Extensive research has been dedicated to preparing membrane spacers with excellent surface properties, potentially improving the membrane filtration performance for water remediation. The revolutionary developments in membrane module fabrication have driven the utilization of 3D printing approaches toward manufacturing advanced membrane components, including biocarriers, sorbents, catalysts, and even whole membranes. This perspective highlights recent advances and essential outcomes in 3D printing technologies for wastewater treatment. First, different 3D printing techniques, such as material extrusion, selective laser sintering (SLS), and vat photopolymerization, emphasizing membrane fabrication, are briefly discussed. Importantly, in this Perspective, we focus on the unique 3D-printed membrane modules, namely, feed spacers, biocarriers, sorbents, and so on. The unparalleled advantages of 3D printed membrane components in surface area, geometry, and thickness and their influence on antifouling, removal efficiency, and overall membrane performance are underlined. Moreover, the salient applications of 3D printing technologies for water desalination, oil-water separation, heavy metal and organic pollutant removal, and nuclear decontamination are also outlined. This Perspective summarizes the recent works, current limitations, and future outlook of 3D-printed membrane technologies for wastewater treatment.

NIR-activated quercetin-based nanogels embedded with CuS nanoclusters for the treatment of drug-resistant biofilms and accelerated chronic wound healing.

We have developed multifunctional nanogels with antimicrobial, antioxidant, and anti-inflammatory properties, facilitating rapid wound healing. To prepare the multifunctional nanogels, we utilized quercetin (Qu) and a mild carbonization process to form carbonized nanogels (CNGs). These CNGs possess excellent antioxidative and bacterial targeting properties. Subsequently, we utilized the Qu-CNGs as templates to prepare nanogels incorporating copper sulfide (CuS) nanoclusters, further enhancing their functionality. Notably, the CuS/Qu-CNGs nanocomposites demonstrated an exceptional minimum inhibitory concentration against tested bacteria, approximately 125-fold lower than monomeric Qu or Qu-CNGs. This enhanced antimicrobial effect was achieved by leveraging near-infrared II (NIR-II) light irradiation. Additionally, the CuS/Qu-CNGs exhibited efficient penetration into the extracellular biofilm matrix, eradicating methicillin-resistant Staphylococcus aureus-associated biofilms in diabetic mice wounds. Furthermore, the nanocomposites were found to suppress proinflammatory cytokines, such as IL-1ß, at the wound sites while regulating the expression of anti-inflammatory factors, including IL-10 and TGF-ß1, throughout the recovery process. The presence of CuS/Qu-CNGs promoted angiogenesis, epithelialization, and collagen synthesis, thereby accelerating wound healing. Our developed CuS/Qu-CNGs nanocomposites have great potential in addressing the challenges associated with delayed wound healing caused by microbial pathogenesis.

Pulsed laser irradiation induces the generation of alloy cluster ions for the screening of protease activity.

Pulsed laser irradiation can cause the fragmentation of nanoparticles, which generates cluster ions. This allows nanoparticles to be adopted as mass tag/signal amplifiers in laser desorption/ionization mass spectrometry (LDI-MS) bioassays. Herein, we demonstrate the potential of using the signal from alloy cluster ions in bioassays through a fibrin clot model to determine the activity of thrombin. A mixed solution of silver and gold nanoparticles functionalized with fibrinogen (Fg‒Ag NPs/Fg‒Au NPs) treated with thrombin can form clots composed of aggregated fibrin-Au NPs/Ag NPs. These clots analyzed with LDI-MS are noted to form intense Ag-Au alloy cluster ions, especially [Ag2Au]+, which were used to detect thrombin concentration with a dynamic range of 2.5-50 pM in human plasma. This sensing platform was further employed for the screening of direct thrombin inhibitors. This work developed a novel bioassay utilizing metallic gas-phase reactions generated from pulsed laser irradiation of aggregated nanoparticles to monitor enzymatic activity and to screen inhibitors. We believe that LDS-MS can serve as a new platform for gas-phase reaction-based bioassays.

Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment.

Bacteremia and associated bacterial sepsis are potentially fatal and occur when the host response to microbial invasion is impaired or compromised. This motivated us to develop carbonized polymer dots (CPDsMan/AA) from a mixture of mannose (Man) and positively charged amino acids [AAs; lysine, arginine (Arg), or histidine] through a one-step mild pyrolysis procedure, which effectively inhibited drug-resistant bacterial strains isolated from septic patients. The as-prepared CPDsMan/AA showed broad-spectrum antibacterial activity, including multidrug-resistant bacteria, even in human plasma. The minimal inhibitory concentration of CPDsMan/Arg is ca. 1.0 µg mL-1, which is comparable to or lower than those of other tested antibiotics (e.g., ampicillin, gentamicin, and vancomycin). In addition to directly disrupting bacterial membranes, the CPDsMan/Arg feature a structure similar to aminoglycoside antibiotics that could bind to 16S rRNA, thereby blocking bacterial protein synthesis. In vitro cytotoxic and hemolytic assays demonstrated the high biocompatibility of the CPDsMan/AA. In addition, in vivo studies on methicillin-resistant Staphylococcus aureus-infected mice treated with the CPDsMan/Arg showed a significant decrease in mortality-even better than that of antibiotics. Overall, the synthesis of the CPDsMan/AA is cost-efficient, straightforward, and effective for treating bacteremia. The polymeric features of the CPDsMan/Arg, including cationic charges and specific groups, can be recognized as a safe and broad-spectrum biocide to lessen our reliance on antibiotics to treat systemic bacterial infections in the future.

Recent progress in nanomaterial-functionalized membranes for removal of pollutants.

Membrane technology has gained tremendous attention for removing pollutants from wastewater, mainly due to their affordable capital cost, miniature equipment size, low energy consumption, and high efficiency even for the pollutants present in lower concentrations. In this paper, we review the literature to summarize the progress of nanomaterial-modified membranes for wastewater treatment applications. Introduction of nanomaterial in the polymeric matrix influences membrane properties such as surface roughness, hydrophobicity, porosity, and fouling resistance. This review also covers the importance of functionalization strategies to prepare thin-film nanocomposite hybrid membranes and their effect on eliminating pollutants. Systematic discussion regarding the impact of the nanomaterials incorporated within membrane, toward the recovery of various pollutants such as metal ions, organic compounds, dyes, and microbes. Successful examples are provided to show the potential of nanomaterial-functionalized membranes for regeneration of wastewater. In the end, future prospects are discussed to develop nanomaterial-based membrane technology.

Self-redox reaction driven in situ formation of Cu2O/Ti3C2Tx nanosheets boost the photocatalytic eradication of multi-drug resistant bacteria from infected wound.

BACKGROUND: MXenes with interesting optical and electrical properties have been attractive in biomedical applications such as antibacterial and anticancer agents, but their low photogeneration efficiency of reactive oxygen species (ROS) and poor stability are major concerns against microbial resistance. METHODS: Water-dispersible single layer Ti3C2Tx-based MXene through etching tightly stacked MAX phase precursor using a minimally intensive layer delamination method. After addition of Cu(II) ions, the adsorbed Cu(II) ions underwent self-redox reactions with the surface oxygenated moieties of MXene, leading to in situ formation of Cu2O species to yield Cu2O/Ti3C2Tx nanosheets (heterostructures). RESULTS: Under NIR irradiation, the Cu2O enhanced generation of electron-hole pairs, which boosted the photocatalytic production of superoxide and subsequent transformation into hydrogen peroxide. Broad-spectrum antimicrobial performance of Cu2O/Ti3C2Tx nanosheets with sharp edges is attributed to the direct contact-induced membrane disruption, localized photothermal therapy, and in situ generated cytotoxic free radicals. The minimum inhibitory concentration of Cu2O/Ti3C2Tx nanosheets reduced at least tenfold upon NIR laser irradiation compared to pristine Cu2O/Ti3C2Tx nanosheets. The Cu2O/Ti3C2Tx nanosheets were topically administrated on the methicillin-resistant Staphylococcus aureus (MRSA) infected wounds on diabetic mice. CONCLUSION: Upon NIR illumination, Cu2O/Ti3C2Tx nanosheets eradicated MRSA and their associated biofilm to promote wound healing. The Cu2O/Ti3C2Tx nanosheets with superior catalytic and photothermal properties have a great scope as an effective antimicrobial modality for the treatment of infected wounds.

Evaluation of chemotherapeutic response in living cells using subcellular Organelle‒Selective amphipathic carbon dots.

Monitoring of structural changes in subcellular organelles is critical to evaluate the chemotherapeutic response of cells. However, commercial organelle selective fluorophores are easily photobleached, and thus are unsuitable for real-time and long-term observation. We have developed photostable carbon-dot liposomes (CDsomes)-based fluorophores for organellar and suborganellar imaging to circumvent these issues. The CDs synthesized through a mild pyrolysis/hydrolysis process exhibit amphipathic nature and underwent self-assembly to form liposome-like structures (CDsomes). The controlled hydrophilicity or hydrophobicity-guided preparation of CDsomes are used to selectively and rapidly (<1 min) stain nucleolus, cytoplasm, and membrane. In addition, the CDsomes offer universal high-contrast staining not only in fixed cells but also in living cells, allowing real-time observation and morphological identification in the specimen. The as-prepared CDsomes exhibit excitation-dependent fluorescence, and are much more stable under photoirradiation (e.g., ultraviolet light) than traditional subcellular dyes. Interestingly, the CDsomes can be transferred to daughter cells by diluting the particles, enabling multigenerational tracking of suborganelle for up to six generations, without interrupting the staining pattern. Therefore, we believe that the ultra-photostable CDsomes with high biocompatibility, and long-term suborganellar imaging capabilities, hold a great potential for screening and evaluating therapeutic performance of various chemotherapeutic drugs.

Multifunctional carbonized nanogels to treat lethal acute hepatopancreatic necrosis disease.

BACKGROUND: Shrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteria Vibrio parahaemolyticus (V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse. METHODS: Mild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 â„ƒ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules. RESULTS: DAO/DEX-CNGs manifest broad-spectrum antibacterial activity against Vibrio parahaemolyticus responsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition of Vibrio in the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severe V. parahaemolyticus infection, revealing that CNGs can effectively guard shrimp from Vibrio invasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed. CONCLUSION: Our work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti-Vibrio agents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture.

Catalytic and photoresponsive BiZ/CuxS heterojunctions with surface vacancies for the treatment of multidrug-resistant clinical biofilm-associated infections.

We report a one-pot facile synthesis of highly photoresponsive bovine serum albumin (BSA) templated bismuth-copper sulfide nanocomposites (BSA-BiZ/CuxS NCs, where BiZ represents in situ formed Bi2S3 and bismuth oxysulfides (BOS)). As-formed surface vacancies and BiZ/CuxS heterojunctions impart superior catalytic, photodynamic and photothermal properties. Upon near-infrared (NIR) irradiation, the BSA-BiZ/CuxS NCs exhibit broad-spectrum antibacterial activity, not only against standard multidrug-resistant (MDR) bacterial strains but also against clinically isolated MDR bacteria and their associated biofilms. The minimum inhibitory concentration of BSA-BiZ/CuxS NCs is 14-fold lower than that of BSA-CuxS NCs because their multiple heterojunctions and vacancies facilitated an amplified phototherapeutic response. As-prepared BSA-BiZ/CuxS NCs exhibited substantial biofilm inhibition (90%) and eradication (>75%) efficiency under NIR irradiation. Furthermore, MRSA-infected diabetic mice were immensely treated with BSA-BiZ/CuxS NCs coupled with NIR irradiation by destroying the mature biofilm on the wound site, which accelerated the wound healing process via collagen synthesis and epithelialization. We demonstrate that BSA-BiZ/CuxS NCs with superior antimicrobial activity and high biocompatibility hold great potential as an effective photosensitive agent for the treatment of biofilm-associated infections.

Copper Sulfide Nanoassemblies for Catalytic and Photoresponsive Eradication of Bacteria from Infected Wounds.

Bovine serum albumin (BSA)-encapsulated copper sulfide nanocrystals (CuS NCs) were prepared by heating an alkaline solution containing copper ions and BSA without an additional sulfur source. At a high BSA concentration (0.8 mM), nanoassembly of the as-formed CuS NCs occurs to form BSA-CuS NCs as a result of the formation of BSA gel-like structures. In addition to their intrinsic photothermal properties, the BSA-CuS NCs possess rich surface vacancies and thus exhibit enzyme-like and photodynamic activities. Spontaneous generation of hydrogen peroxide (H2O2) led to the in situ formation of copper peroxide (CPO) nanodots on the BSA-CuS NCs to catalyze singlet oxygen radical generation. The antimicrobial response was enhanced by >60-fold upon NIR laser irradiation, which was ascribed to the combined effect of the photodynamic and photothermal inactivation of bacteria. Furthermore, BSA-CuS NCs were transdermally administered onto a methicillin-resistant Staphylococcus aureus-infected wound and eradicated >99% of bacteria in just 1 min under NIR illumination due to the additional peroxidase-like activity of BSA-CuS NCs, transforming H2O2 at the infection site into hydroxyl radicals and thus increasing the synergistic effect from photodynamic and photothermal treatment. The BSA-CuS NCs exhibited insignificant in vitro cytotoxicity and hemolysis and thus can serve as highly biocompatible bactericides in preclinical applications to effectively eradicate bacteria.

Self-Sufficient and Highly Efficient Gold Sandwich Upconversion Nanocomposite Lasers for Stretchable and Bio-applications.

Multifunctional lanthanide-doped upconversion nanoparticles (UCNPs) have spread their wings in the fields of flexible optoelectronics and biomedical applications. One of the ongoing challenges lies in achieving UCNP-based nanocomposites, which enable a continuous-wave (CW) laser action at ultralow thresholds. Here, gold sandwich UCNP nanocomposites [gold (Au1)-UCNP-gold (Au2)] capable of exhibiting lasing at ultralow thresholds under CW excitation are demonstrated. The metastable energy-level characteristics of lanthanides are advantageous for creating population inversion. In particular, localized surface plasmon resonance-based electromagnetic hotspots in the nanocomposites and the huge enhancement of scattering coefficient for the formation of coherent closed loops due to multiple scattering facilitate the process of stimulated emissions as confirmed by theoretical simulations. The nanocomposites are subjected to stretchable systems for enhancing the lasing action (threshold ∼ 0.06 kW cm-2) via a light-trapping effect. The applications in bioimaging of HeLa cells and antibacterial activity (photothermal therapy) are demonstrated using the newly designed Au1-UCNP-Au2 nanocomposites.

Capping 1,3-propanedithiol to boost the antibacterial activity of protein-templated copper nanoclusters.

We have prepared copper nanoclusters (Cu NCs) in the presence of bovine serum albumin (BSA) and 1,3-propanedithiol (PDT). The PDT/BSA-Cu NCs possess great activities against different types of bacteria, including non-multidrug-resistant bacteria (Escherichia coli, Salmonella Enteritidis, Pseudomonas aeruginosa, and Staphylococcus aureus) and multidrug-resistant bacteria (methicillin-resistant S. aureus). Their minimal inhibitory concentration (MIC) values are at least 242-fold and 10-fold lower than that of the free PDT and BSA-Cu NCs, respectively. The PDT/BSA-Cu NCs are strongly bound to the bacterial membrane, in which they induce the generation of ascorbyl (Asc) and perhydroxyl (HOO) radicals that result in disruption of their membrane integrity. At a concentration of 100-fold higher than their MIC for Escherichia coli, the PDT/BSA-Cu NCs exhibit negligible cytotoxicity towards the tested mammalian cells and show insignificant hemolysis. We have further demonstrated that low-cost PDT/BSA-Cu NCs-coated carbon fiber fabrics (CFFs) are effective against antibacterial growth, showing their great potential for antifouling applications.

Dendrimer as a multifunctional capping agent for metal nanoparticles for use in bioimaging, drug delivery and sensor applications.

Advances in nanoparticle research, particularly in the domain of surface-engineered, function-oriented nanoparticles, have had a profound effect in many areas of scientific research and aided in bringing unprecedented developments forward, particularly in the biomedical field. Surface modifiers/capping agents have a direct bearing on the major properties of metal nanoparticles (MNPs), ranging from their physico-chemical properties to their stability and functional applications. Among the different classes of capping agents, dendrimers have gained traction as effective multifunctional capping agents for MNPs due to their unique structural qualities, dendritic effect and polydentate nature. Dendrimer-coated metal nanoparticles (DC-MNPs) are typically produced by both (i) a one-pot strategy, where metal ions are reduced in the presence of dendrimer molecules and (ii) a multi-pot strategy, where a sequence of reactions involving the reduction of metal ions, activation, conjugation and purification steps are involved. These DC-MNPs have shown remarkable ability to stabilize MNPs by means of electrostatic interactions, coordination chemistry or covalent attachment, due to them entailing a large number of sites at which further molecular moieties can be conjugated. This review article is an attempt to consolidate the on-going work, particularly over the last five years, in the field of the synthesis of dendrimer-coated MNPs and their potential applications in bioimaging, drug delivery and biochemical sensors.