High-throughput fluorescence sensing array based on tetraphenylethylene derivatives for detecting and distinguishing pathogenic microbes.

Infections induced by pathogenic microorganisms will bring negative effects such as diseases that damage health and result in heavy economic burden. Therefore, it is very important to detect and identify the pathogens in time. Moreover, traditional clinical diagnosis or food testing often faces the problem of dealing with a large number of samples. Here, we designed a high-throughput fluorescent sensor array based on the different binding ability of five tetraphenylethylene derivatives (TPEs) with various side chains to different kinds of pathogenic microbes, which is used to detect and distinguish various species, so as to realize rapid mass diagnosis, and hopefully provide guidance for further determination of microbial infections and clinical treatment.

Construction of gelatin/alginate hydrogels doped hemicyanine derivatives for photodynamic antibacterial application.

Hydrogel systems based on natural polymer materials have provided alternative opportunities for preparing antimicrobial dressings. A composite antibacterial hydrogel system containing gelatin (Gel), alginate (Alg) and hemicyanine derivatives with different chain lengths (C3, C6 and C10) was constructed. The composite hydrogels have excellent swelling ability and low degradability due to the classical three-dimensional network structure. Because of the photosensitization ability of C3, C6 and C10, hydrogels containing these molecules can also effectively produce reactive oxygen species (ROS) under light. Importantly, the hydrogel containing C3 molecules that have higher spatial extension structure and shorter alkyl chain than C6 and C10 shows better photo-responsive antibacterial effect against drug-resistant Escherichia coli. The bacterial killing activity of the composite hydrogel system could be regulated by changing the alkyl chain length of the photosensitizers. This effective and photo-responsive composite hydrogel system is expected to be used for bacteria-infected wound repair and promoting wound healing.

Burgeoning Single-Atom Nanozymes for Efficient Bacterial Elimination.

To fight against antibacterial-resistant bacteria-induced infections, the development of highly efficient antibacterial agents with a low risk of inducing resistance is exceedingly urgent. Nanozymes can rapidly kill bacteria with high efficiency by generating reactive oxygen species via enzyme-mimetic catalytic reactions, making them promising alternatives to antibiotics for antibacterial applications. However, insufficient catalytic activity greatly limits the development of nanozymes to eliminate bacterial infection. By increasing atom utilization to the maximum, single-atom nanozymes (SAzymes) with an atomical dispersion of active metal sites manifest superior enzyme-like activities and have achieved great results in antibacterial applications in recent years. In this review, the latest advances in antibacterial SAzymes are summarized, with specific attention to the action mechanism involved in antibacterial applications covering wound disinfection, osteomyelitis treatment, and marine antibiofouling. The remaining challenges and further perspectives of SAzymes for practical antibacterial applications are also discussed.

Recent Advances of Composite Nanomaterials for Antibiofilm Application.

A biofilm is a microbial community formed by bacteria that adsorb on the surface of tissues or materials and is wrapped in extracellular polymeric substances (EPS) such as polysaccharides, proteins and nucleic acids. As a protective barrier, the EPS can not only prevent the penetration of antibiotics and other antibacterial agents into the biofilm, but also protect the bacteria in the biofilm from the attacks of the human immune system, making it difficult to eradicate biofilm-related infections and posing a serious threat to public health. Therefore, there is an urgent need to develop new and efficient antibiofilm drugs. Although natural enzymes (lysozyme, peroxidase, etc.) and antimicrobial peptides have excellent bactericidal activity, their low stability in the physiological environment and poor permeability in biofilms limit their application in antibiofilms. With the development of materials science, more and more nanomaterials are being designed to be utilized for antimicrobial and antibiofilm applications. Nanomaterials have great application prospects in antibiofilm because of their good biocompati-bility, unique physical and chemical properties, adjustable nanostructure, high permeability and non-proneness to induce bacterial resistance. In this review, with the application of composite nanomaterials in antibiofilms as the theme, we summarize the research progress of three types of composite nanomaterials, including organic composite materials, inorganic materials and organic-inorganic hybrid materials, used as antibiofilms with non-phototherapy and phototherapy modes of action. At the same time, the challenges and development directions of these composite nanomaterials in antibiofilm therapy are also discussed. It is expected we will provide new ideas for the design of safe and efficient antibiofilm materials.

Recent Strategies to Develop Conjugated Polymers for Detection and Therapeutics.

The infectious diseases resulting from pathogenic microbes are highly contagious and the source of infection is difficult to control, which seriously endangers life and public health safety. Although the emergence of antibiotics has a good therapeutic effect in the early stage, the massive abuse of antibiotics has brought about the evolution of pathogens with drug resistance, which has gradually weakened the lethality and availability of antibiotics. Cancer is a more serious disease than pathogenic bacteria infection, which also threatens human life and health. Traditional treatment methods have limitations such as easy recurrence, poor prognosis, many side effects, and high toxicity. These two issues have led to the exploration and development of novel therapeutic agents (such as conjugated polymers) and therapeutic strategies (such as phototherapy) to avoid the increase of drug resistance and toxic side effects. As a class of organic polymer biological functional materials with excellent photoelectric properties, Conjugated polymers (CPs) have been extensively investigated in biomedical fields, such as the detection and treatment of pathogens and tumors due to their advantages of easy modification and functionalization, good biocompatibility and low cost. A rare comprehensive overview of CPs-based detection and treatment applications has been reported. This paper reviews the design strategies and research status of CPs used in biomedicine in recent years, introduces and discusses the latest progress of their application in the detection and treatment of pathogenic microorganisms and tumors according to different detection or treatment methods, as well as the limitations and potential challenges in prospective exploration.

Construction of Electrostatic Spinning Membranes Based on Conjugated Hemicyanine Derivatives for Photodynamic Antibacterial Application.

The preparation of efficient antibacterial membrane materials is one of the important strategies to fight against bacterial infection and alleviate drug resistance. Herein, hemicyanine derivatives with different chain lengths (C3, C6, and C10) that exhibit excellent photodynamic antibacterial activity were doped into spinnable polyvinyl alcohol solution (PVA, 8%) to obtain composite fiber membrane Cn/PVA (C3/PVA, C6/PVA, and C10/PVA) by a simple "one-pot" method using electrospinning technology. The antibacterial nanofiber membrane has a dense fiber structure which has a good interception effect, high thermal stability, and great biocompatibility. Importantly, Cn/PVA nanofibers could efficiently sensitize oxygen to generate reactive oxygen species (ROS), leading to high photokilling efficacy against drug-resistant bacteria. The variation of structure for hemicyanines causes the difference of Cn/PVA nanofibers in the effects of antibacterial performance, and it is found that C3/PVA and C10/PVA with three and ten carbons in the alkyl chain could kill more than 97% of ampicillin-resistant E. coli, which is much better than that of C6/PVA. Moreover, C3/PVA and C10/PVA exhibited killing efficiencies of 98.6 and 90.6% against MRSA, respectively. The construction of Cn/PVA composite fibers provides research ideas for the development of structure-dependent antimicrobial surface materials and is expected to be applied as superficial medical antibacterial protection materials.

Recent Progress of Photothermal Therapy Based on Conjugated Nanomaterials in Combating Microbial Infections.

Photothermal therapy has the advantages of non-invasiveness, low toxicity, simple operation, a broad spectrum of antibacterial ability, and non-proneness to developing drug resistance, which provide it with irreplaceable superiority in fighting against microbial infection. The effect of photothermal therapy is closely related to the choice of photothermal agent. Conjugated nanomaterials are potential candidates for photothermal agents because of their easy modification, excellent photothermal conversion efficiency, good photostability, and biodegradability. In this paper, the application of photothermal agents based on conjugated nanomaterials in photothermal antimicrobial treatment is reviewed, including conjugated small molecules, conjugated oligomers, conjugated polymers, and pseudo-conjugated polymers. At the same time, the application of conjugated nanomaterials in the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) is briefly introduced. Finally, the research status, limitations, and prospects of photothermal therapy using conjugated nanomaterials as photothermal agents are discussed.

Recent Advances of Natural-Polymer-Based Hydrogels for Wound Antibacterial Therapeutics.

Hydrogels have a three-dimensional network structure and high-water content, are similar in structure to the extracellular matrix, and are often used as wound dressings. Natural polymers have excellent biocompatibility and biodegradability and are commonly utilized to prepare hydrogels. Natural-polymer-based hydrogels can have excellent antibacterial and bioactive properties by loading antibacterial agents or being combined with therapeutics such as phototherapy, which has great advantages in the field of treatment of microbial infections. In the published reviews of hydrogels used in the treatment of infectious wounds, the common classification criteria of hydrogels include function, source of antibacterial properties, type of antibacterial agent, etc. However, there are few reviews on the classification of hydrogels based on raw materials, and the description of natural-polymer-based hydrogels is not comprehensive and detailed. In this paper, based on the principle of material classification, the characteristics of seven types of natural polymers that can be used to prepare hydrogels are discussed, respectively, and the application of natural-polymer-based hydrogels in the treatment of infectious wounds is described in detail. Finally, the research status, limitations, and prospects of natural-polymer-based hydrogels are briefly discussed.

Triazine-Porphyrin-Based Hyperconjugated Covalent Organic Framework for High-Performance Photocatalysis.

Covalent organic frameworks (COFs) with porphyrins as structural units are a new kind of porous organic polymers, which have a regular and ordered structure, abundant porosity, and good stability. In the past, the construction of porphyrin COFs was generally synthesized by routes such as a Schiff base reaction. Here, we report a new COF structure by linking the porphyrin with the triazine ring. Using a cyano group-terminated porphyrin as a structural unit precursor, a new triazine-porphyrin hyperconjugated COF (TA-Por-sp2-COF) was constructed through the cyano group's self-polymerization. The extension of porphyrin units in two directions that stemmed from the cyano group at para-positions accounts for the establishment of a highly ordered two-dimensional topological structure. Attributing to the collaboration of electron-donating and withdrawing blocks for photo-induced carrier separation and adequate porosity for mass diffusion, this hyperconjugated system showed high photocatalytic performance in organic reactions such as the aerobic coupling reaction of benzylamine and thioanisole selective oxidation.

Regulation of Antimicrobial Effect of Hemicyanine-Based Photosensitizer via Supramolecular Assembly.

An intelligent "antimicrobial switch" has been constructed to reduce prolonged exposure of pathogenic bacteria to antibiotics, which could reversibly "turn off" or "turn on" the antimicrobial activity of hemicyanines through self-assembly or dis-assembly of cucurbit[7]uril (CB[7]). This assembly effectively inhibited the production of ROS under light, shielding the active site of hemicyanines and achieving on-demand antimicrobial ability. Moreover, CB[7] differentially inhibits ROS of molecules with different alkyl chain lengths, which provided reference for the subsequent design of materials with antimicrobial activity regulation, and could effectively delay or even prevent the development of pathogens resistance.

Photodynamic Antimicrobial Therapy Based on Conjugated Polymers.

Pathogenic microorganisms have been a serious threat to human life and have become a public health problem of global concern. However, in the actual treatment there is a lack of efficient antimicrobial strategies which do not easily develop drug resistance; this can lead to inaccurate drug treatment that worsens the infection and even threatens life. With the emergence of a variety of drug-resistant bacteria and fungi, photodynamic therapy has gradually become one of the most promising treatment methods for drug-resistant bacteria infection; this is because it is controllable, non-invasive, and not prone to cause the development of drug resistance. Organic conjugated polymers that possess high fluorescence intensity, a large molar extinction coefficient, excellent light stability, an adjustable energy band, easy modification, good biocompatibility, and the ability to photosensitize oxygen to produce reactive oxygen species have been widely used in the fields of solar cells, highly sensitive detection systems, biological imaging, and anti-cancer and anti-microbial treatment. Photodynamic therapy is non-invasive and has high temporal and spatial resolution and is a highly effective antimicrobial treatment that does not easily induce drug resistance; it has also stimulated the scientific research enthusiasm of researchers and has become a research hotspot in the antimicrobial field. In this review, the photodynamic antibacterial applications of conjugated polymers with different structure types are summarized, and their development directions are considered.

Assembly of Hexagonal Column Interpenetrated Spheres from Plant Polyphenol/Cationic Surfactants and Their Application as Antimicrobial Molecular Banks.

Microbial infections have become a great threat to human health and one of the main risks arises from direct contact with the surfaces contaminated by pathogenic microbes. Herein, a kind of hexagonal column interpenetrated spheres (HCISs) are fabricated by non-covalent assembly of plant gallic acid with quaternary ammonium surfactants. Different from one-time burst release of conventional antimicrobial agents, the HCIS acts like a "antimicrobial molecular bank" and releases the antimicrobial ingredients in a multistage way, leading to long-lasting antimicrobial performance. Taking advantage of strong hydrophobicity and adhesion, HCISs are applicable to various substrates and endowed with anti-water washing property, thus showing high in vitro antimicrobial efficiency (>99 %) even after being used for 10 cycles. Meanwhile, HCISs exhibit broad-spectrum antimicrobial activity against bacteria and fungi, and have good biocompatibility with mammalian cells. Such a low-cost and portable long-lasting antimicrobial agent meets the growing anti-infection demand in public spaces.

Sulfur-Doped BiOCl with Enhanced Light Absorption and Photocatalytic Water Oxidation Activity.

Photocatalysis is a powerful strategy to address energy and environmental concerns. Sulfur-doped BiOCl was prepared through a facial hydrothermal method to improve the photocatalytic performance. Experimental results and theoretical calculations demonstrated that the band structure of the sulfur-doped BiOCl was optimally regulated and the light absorption range was expanded. It showed excellent visible-light photocatalytic water oxidation properties with a rate of 141.7 µmol h-1 g-1 (almost 44 times of that of the commercial BiOCl) with Pt as co-catalyst.

Supramolecular Regulation of Catalytic Activity for an Amphiphilic Pyrene-Ruthenium Complex in Water.

A switchable catalytic system has been designed and constructed with a host-guest interaction between cucurbituril (CB) and an amphiphilic metal complex pyrene-ruthenium (Py-Ru). Py-Ru can self-assemble into positively charged nanoparticles in water, and exhibits an enhanced catalytic efficiency in the transfer hydrogenation of NAD+ to NADH. After forming an inclusion complex with CB, Py-Ru aggregates are broken, leading to a decrease in catalytic efficiency, which can be recovered by competitive replacement with amantadine. This supramolecular strategy provides an efficient and flexible method for constructing reversible catalytic system, which also extends the application scope of the host-guest interaction.

3D Bioprinting of Polythiophene Materials for Promoting Stem Cell Proliferation in a Nutritionally Deficient Environment.

3D printing of stem cells provides a tremendous opportunity to tissue engineering in regenerative medicine. However, developing new bioactive materials to rationally augment stem cell viability is still an enormous challenge owing to the nutritionally deficient environment caused by the limited-penetration distance of nutrition when cells are encapsulated within biomaterials. In this work, a cationic conjugated polythiophene derivative, poly[3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene hydrochloride] (PMNT), is designed and integrated into an anionic gelatin/alginate matrix to develop a new 3D bioprintable conjugated polymer ink Gel/Alg/PMNT, while the electrostatic interaction can assist PMNT to anchor inside ink without severe diffusional loss. In principle, PMNT is confirmed to promote human umbilical cord-derived mesenchymal stem cell (hMSC) proliferation in a serum-free medium by driving cell cycles and up-regulating gene expression in the pathways of biosynthesis and the metabolism. By employing the 3D bioprinting strategy together with hMSCs, the accelerated healing of full-thickness excisional wounds is further realized through the augmented-stem cell therapeutics utilizing Gel/Alg/PMNT ink, in which hMSC proliferation can be effectively promoted upon inductive stimulation of PMNT. The inherent highly bioactive and robust proliferation-promoted nature of the developed conjugated polymer ink Gel/Alg/PMNT significantly overcomes the nutritionally deficient environment, especially in 3D-printed large-scale architectures. The bioactive polythiophene material exhibits a unique capacity to promote stem cell proliferation without the need of serum, providing a new bioink for 3D bioprinting in tissue reconstructions.

Direct Observation of Metal Oxide Nanoparticles Being Transformed into Metal Single Atoms with Oxygen-Coordinated Structure and High-Loadings.

Direct conversion of bulk metal or nanoparticles into metal single atoms under thermal pyrolysis conditions is a highly efficient and promising strategy to fabricate single-atom catalysts (SACs). Usually, nitrogen-doped carbon is used as the anchoring substrate to capture the migrating metal ion species at high temperatures, and stable isolated SACs with nitrogen coordination are formed during the process. Herein, we report unexpected oxygen-coordinated metal single-atom catalysts (Fe-, Co-, Ni-, Mn-SACs) with high loadings (above 10 wt %) through direct transformation of metal oxide nanoparticles (Fe-, Co-, Ni-, Mn-NPs) in an inert atmosphere at 750 °C for 2 h. The atomic dispersion of metal single atoms and their coordinated structures were confirmed by aberration-corrected scanning transmission electron microscopy and X-ray absorption fine structures. In addition, the dynamic process of nanoparticles to atoms was directly observed by in situ transmission electron microscopy. The as-prepared Fe SAC exhibited high activity and superior selectivity for catalytic oxidation of benzene to phenol with hydrogen peroxide.

Sensitive Detection and Conjoint Analysis of Promoter Methylation by Conjugated Polymers for Differential Diagnosis and Prognosis of Glioma.

Glioma is the most common primary tumor in the central nervous system (CNS) with the worst prognosis. Accurate pathological diagnosis has always been a challenge for optimal management of glioma. Promoter methylation is an important mechanism of epigenetic silencing tumor-suppressor genes and a potential biomarker for differential diagnosis and prognosis. Herein, using the cationic conjugated polymer (CCP)-based fluorescence resonance energy transfer (FRET) technique, we realized a highly sensitive detection of promoter methylation in clinical samples of minimal methylation degree (1.25%) and trace DNA quantity (10 ng/µL). Results for three glioma-related genes (MGMT, CDKN2A, and TERT) were combined in a diagnostic classifier to analyze the glioma-CpG island methylator phenotype (G-CIMP), which achieved a sensitivity of 80% at a maximum specificity of 100% for a glioma diagnosis. Kaplan-Meier survival curves and Pearson correlation analysis revealed that the prognosis of glioma patients with high G-CIMP scores (>5) was significantly better than those with low G-CIMP scores, especially in diffuse midline glioma and astrocytoma. This CCP-based FRET technique for determining G-CIMP status could provide patients with rapid and reasonably accurate diagnosis of glioma, as well as a valuable prognostic prediction that can guide individual treatment.

In Situ Synthesis of Photoactive Polymers on a Living Cell Surface via Bio-Palladium Catalysis for Modulating Biological Functions.

Cell surface engineering with functional polymers is an effective strategy to modulate cell activity. Here, a bio-palladium catalyzed polymerization strategy was developed for in situ synthesis of conjugated polymers on living cell surfaces. Through Sonagashira polymerization, photoactive polyphenyleneethynylene (PPE) is synthesized on the cell surface via cell-generated bio-Pd catalyst. The in situ formed PPE is identified by excellent light-harvest capacity and blue fluorescence on the surfaces of E. coli and C. pyrenoidosa. Besides imaging microbes for tracing the polymerization process, PPE also exhibits enhanced antibacterial activity against E. coli. It can also augment the ATP synthesis of C. pyrenoidosa through enlarging the light absorption and accelerating the cyclic electron transport of the algae. With this bio-metal catalyzed polymerization method, functional polymers can be synthesized in situ on the living cell surface.

Gemini Peptide Amphiphiles with Broad-Spectrum Antimicrobial Activity and Potent Antibiofilm Capacity.

To address the challenge from microbial resistance and biofilm, this work develops three gemini peptide amphiphiles with basic tetrapeptide spacers 12-(Arg)4-12, 12-(Lys)4-12, and 12-(His)4-12 and finds that they exhibit varied antimicrobial/antibiofilm activities. 12-(Arg)4-12 shows the best performance, possessing the broad-spectrum antimicrobial activity and excellent antibiofilm capacity. The antimicrobial and antibiofilm activities strongly depend on the membrane permeation and self-assembling structure of these peptide amphiphiles. Gemini peptide amphiphile with highly polar arginine as the spacer, 12-(Arg)4-12, self-assembles into short rods that are prone to dissociate into monomers for permeating and lysing membrane , leading to its broad-spectrum antimicrobial activity and high efficiency in eradicating biofilm. Long rods formed by relatively weaker polar 12-(Lys)4-12 are less prone to disassemble into monomers for further membrane permeation, which makes it selectively kill more negatively charged bacteria and endow it medium antibiofilm activity. Low polar 12-(His)4-12 aggregates into long fibers, which are very difficult to dissociate and they mainly electrostatically bind on the negative microbial surface, resulting in its weakest antimicrobial and antibiofilm activity. This study reveals the effect of the antimicrobial peptide structure and aggregation on the antimicrobial activities and would be helpful for developing high-efficient antimicrobial peptides with antibiofilm activity.

Fluorescent and Biocompatible Ruthenium-Coordinated Oligo(p-phenylenevinylene) Nanocatalysts for Transfer Hydrogenation in the Mitochondria of Living Cells.

It is challenging to design metal catalysts for in situ transformation of endogenous biomolecules with good performance inside living cells. Herein, we report a multifunctional metal catalyst, ruthenium-coordinated oligo(p-phenylenevinylene) (OPV-Ru), for intracellular catalysis of transfer hydrogenation of nicotinamide adenine dinucleotide (NAD+ ) to its reduced format (NADH). Owing to its amphiphilic characteristic, OPV-Ru possesses good self-assembly capability in water to form nanoparticles through hydrophobic interaction and π-π stacking, and numerous positive charges on the surface of nanoparticles displayed a strong electrostatic interaction with negatively charged substrate molecules, creating a local microenvironment for enhancing the catalysis efficiency in comparison to dispersed catalytic center molecule (TOF value was enhanced by about 15 fold). OPV-Ru could selectively accumulate in the mitochondria of living cells. Benefiting from its inherent fluorescence, the dynamic distribution in cells and uptake behavior of OPV-Ru could be visualized under fluorescence microscopy. This work represents the first demonstration of a multifunctional organometallic complex catalyzing natural hydrogenation transformation in specific subcellular compartments of living cells with excellent performance, fluorescent imaging ability, specific mitochondria targeting and good chemoselectivity with high catalysis efficiency.