Recent Advances in Fluorescent Nanoprobes for Food Safety Detection.

Fluorescent nanoprobes show similar fluorescence properties to traditional organic dyes, but the addition of nanotechnology accurately controls the size, shape, chemical composition, and surface chemistry of the nanoprobes with unique characteristics and properties, such as bright luminescence, high photostability, and strong biocompatibility. For example, modifying aptamers or antibodies on a fluorescent nanoprobe provides high selectivity and specificity for different objects to be tested. Fluorescence intensity, life, and other parameters of targets can be changed by different sensing mechanisms based on the unique structural and optical characteristics of fluorescent nanoprobes. What's more, the detection of fluorescent nanoprobes is cost-saving, simple, and offers great advantages in rapid food detection. Sensing mechanisms of fluorescent nanoprobes were introduced in this paper, focusing on the application progress in pesticide residues, veterinary drug residues, heavy metals, microbes, mycotoxins, and other substances in food safety detection in recent years. A brief outlook for future development was provided as well.

Fluorescent sensor array based on aggregation-induced emission luminogens for pathogen discrimination.

A high-throughput tetraphenylethylene (TPE)-based fluorescent sensor array was constructed for the identification and detection of microorganisms, which utilizes three TPE derivatives with different numbers of cationic side chains to detect and discriminate various microorganisms at concentrations down to 1 × 103 CFU mL-1.

Hydroxyl-PEG-Phosphonic Acid-Stabilized Superparamagnetic Manganese Oxide-Doped Iron Oxide Nanoparticles with Synergistic Effects for Dual-Mode MR Imaging.

The T1-T2 dual-mode contrast agents for magnetic resonance imaging (MRI) can generate self-complementary confirmed T2 and T1 images, hence greatly improving the reliability. Facilely synthesizing nanoparticles with the ultrasensitive contrast property remains extremely challenging in nanoscience. Moreover, uncovering the mechanism correlating the signal enhancements and chemical constituents is vital for designing novel efficient synergistically enhanced T1-T2 dual-mode MRI nanoprobes. Herein, we report a one-pot facile method to synthesize the superparamagnetic manganese oxide-doped iron oxide (Fe3O4/MnO) nanoparticles for T1-T2 dual-mode MR imaging. Under external magnetic field, the local magnetic field intensities of MnO and Fe3O4 could be simultaneously enhanced through embedding MnO into Fe3O4 nanoparticles and hence can cause synergistic T1 and T2 contrast enhancements. Moreover, a novel and facile cost-effective method for large-scale synthesis of hydroxyl-polyethylene glycol-phosphonic acid-stabilizing ligands is designed. The facile synthetic method and surface coating strategy of superparamagnetic Fe3O4/MnO nanoparticles offer an idea for the chemical design and preparation of superparamagnetic nanoparticles with ultrasensitive MRI contrast abilities for disease evaluation and treatment.

Electrochemiluminescence for Electric-Driven Antibacterial Therapeutics.

The employment of physical light sources in clinical photodynamic therapy (PDT) system endows it with a crucial defect in the treatment of deeper tissue lesions due to the limited penetration depth of light in biological tissues. In this work, we constructed for the first time an electric driven luminous system based on electrochemiluminescence (ECL) for killing pathogenic bacteria, where ECL is used for the excitation of photosensitizer instead of a physical light source to produce reactive oxygen species (ROS). We named this new strategy as ECL-therapeutics. The mechanism for the ECL-therapeutics is dependent on the perfect spectral overlap and energy transfer from the ECL generated by luminol to photosensitizer, cationic oligo(p-phenylenevinylene) (OPV), to sensitize the surrounding oxygen molecule into ROS. Furthermore, taking into account the practical application of our ECL-therapeutics, we used flexible hydrogel to replace the liquid system to develop hydrogel antibacterial device. Because the chemical reaction is a slow process in the hydrogel, the luminescence could last for more than 10 min after only electrifying for five seconds. This unique persistent luminescence characteristic with long afterglow life makes them suitable for persistent antibacterial applications. Thus, stretchable and persistent hydrogel devices are designed by integrating stretchable hydrogel, persistent ECL and antibacterial function into hydrogel matrices. This novel strategy avoids the employment of external light source, making it simple, convenient and controllable, which exploits a new field for ECL beyond sensors and also opens up a new model for PDT.

A Supramolecular Antibiotic Switch for Antibacterial Regulation.

A supramolecular antibiotic switch is described that can reversibly "turn-on" and "turn-off" its antibacterial activity on demand, providing a proof-of-concept for a way to regulate antibacterial activity of biotics. The switch relies on supramolecular assembly and disassembly of cationic poly(phenylene vinylene) derivative (PPV) with cucurbit[7]uril (CB[7]) to regulate their different interactions with bacteria. This simple but efficient strategy does not require any chemical modification on the active sites of the antibacterial agent, and could also regulate the antibacterial activity of classical antibiotics or photosensitizers in photodynamic therapy. This supramolecular antibiotic switch may be a successful strategy to fight bacterial infections and decrease the emergence of bacterial resistance to antibiotics from a long-term point of view.

Conjugated polymer nanoparticles: preparation, properties, functionalization and biological applications.

In the past few years, conjugated polymer nanoparticles (CPNs) have been successfully prepared and applied in the biological field because of their unique opto-electronic properties. The rapid development of CPNs is mainly attributed to their simple synthesis procedures and easy separation steps. The advantages of CPNs include high brightness, excellent photostability, low cytotoxicity, high quantum yield and versatile surface modification. The functionalization of CPNs with specific recognition elements imparts them good ability for targeted recognition and imaging in vitro and in vivo. CPNs can be applied to deliver drug and gene, and simultaneously to real-time monitor the release process due to their self-luminous characteristics. Moreover, CPNs can sensitize oxygen molecules to generate reactive oxygen species (ROS) which can kill adjacent bacteria and tumor cells. In this tutorial review, we provide a recent development of the preparation methods, properties, and functionalization strategies of CPNs, especially discussing their biological applications in targeted imaging, drug/gene delivery and biomedicine. The challenges and outlooks in this field will also be discussed.

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.

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.

Cell-penetrating peptides noncovalently modified red phosphorescent nanoparticles for high-efficiency imaging.

The application of long-lived phosphorescence probes in time-resolved luminescence imaging is limited by their low quantum yield in aqueous solutions. However, sensitization of thermally activated delayed fluorescence (TADF) materials can compensate for this limitation while addressing the issue of insufficient proportion of their own long lifetime. In this study, we utilized the characteristics of phosphorescence and TADF materials simultaneously by doping the receptor iridium complex PMD-Ir into the donor TADF polymer PCzDP-20 through donor-receptor doping method, and successfully prepared highly efficient red phosphorescent nanoparticles. The quantum yield of the nanoparticles obtained by this method reaches up to 30%, and the luminescence lifetime can reach several thousand nanoseconds. Additionally, due to the low concentration doping of PMD-Ir, the risk of transition metal toxicity is greatly reduced. Furthermore, we used non-covalent modification with amphiphilic cell-penetrating peptides (CPPs) to increase the cell membrane permeability of the nanoparticles. The CPPs modified nanoparticles achieve in vivo confocal imaging of zebrafish and intracellular time-resolved imaging by its significantly improved bioimaging capabilities. The functional nanoparticles designing method fully utilizes the characteristics of PMD-Ir, PCzDP-20, and CPPs, solving the problems of low quantum yield and poor membrane permeability of Ir-complex nanoparticles. This will greatly promote the development of time-resolved luminescence imaging.

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.

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.

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.

An antioxidative, green and safe nanofibers-based film containing pullulan, sodium hyaluronate and Ganoderma lucidum fermentation for enhanced skincare.

Dry masks made of natural active ingredients that are packaged in sustainable paper and free of irritating additives (e.g. preservatives, stabilizers) are a trend in the concept of healthy skincare, which possess the advantages of portability, safety and environmental friendliness. The bioactive ingredients obtained from natural plant fermentation are gradually becoming an important alternative additive for facial skincare. Herein, a novel dry facial healthcare mask was fabricated by electrospinning incorporating natural ingredients including pullulan (Pu), sodium hyaluronate (SH), and Ganoderma lucidum fermentation (GLF). The morphology, dissolving capacity, bioactivity, and safety of the obtained masks were investigated in vitro, and their antioxidation and moisturizing activities were verified at the cellular level. The results indicated that the fibrillary films based on pullulan could be dissolved in water within 20 s with good water retention capacity and film with high concentration of GLF (Pu/SH/GLF-3) could scavenge 79 % of DPPH. The films had good ability to resist microbial contamination and non-eye irritation via observing colony growth for 12 months after ultraviolet sterilization and the ocular irritation test of chicken chorioallantoic membrane. Meanwhile, cell experiments further confirmed that they did not exhibit cytotoxicity and could increase the expression of proteins related to moisturizing and antioxidation. The fascinating films have promising application prospects in cosmetic masks. This work may enrich the use of natural materials in skincare products and provide a green development direction for the light chemical industry.

Chemical molecule-induced light-activated system for anticancer and antifungal activities.

Except for chemotherapy, surgery, and radiotherapy, photodynamic therapy (PDT) as new therapy modality is already in wide clinic use for the treatment of various diseases. The major bottleneck of this technique is the requirement of outer light source, which always limits effective application of PDT to the lesions in deeper tissue. Here, we first report a new modality for treating cancer and microbial infections, which is activated by chemical molecules instead of outer light irradiation. In this system, in situ bioluminescence of luminol can be absorbed by a cationic oligo(p-phenylene vinylene) (OPV) that acts as the photosensitizer through bioluminescence resonance energy transfer (BRET) process. The excited OPV sensitizes oxygen molecule in the surroundings to produce reactive oxygen species (ROS) that kill the adjacent cancer cells in vitro and in vivo, and pathogenic microbes. By avoiding the use of light irradiation, this work opens a new therapy modality to tumor and pathogen infections.

Design and structural regulation of AIE photosensitizers for imaging-guided photodynamic anti-tumor application.

In recent years, photodynamic therapy (PDT) has become one of the important therapeutic methods for treating cancer. Aggregation-induced emission (AIE) photosensitizers (PSs) overcome the aggregation-caused quenching (ACQ) effects of conventional PSs in aggregation or high concentration states, showing enhanced reactive oxygen species (ROS) generating capacity and improved therapeutic efficiency. Meanwhile, connecting different donor and acceptor groups gives the PSs a lower energy level and the absorption/emission of a long wavelength, which makes the PSs produce more ROS and penetrate deeper into the tissue for imaging. As a promising tool for achieving efficient PDT applications, numerous studies have demonstrated the advantages and potential medical applications of AIE PSs in the diagnosis and treatment of various diseases. Herein, we outline the research progress of AIE PSs with different representative structures in fluorescence imaging and photodynamic anti-tumor therapy, and expound the design strategy of the donor-acceptor (D-A) framework for constructing practical AIE PSs in the past three years. Furthermore, this review addresses the underlying challenges and opportunities of AIE PSs in PDT, aiming to grasp the striving directions of the next generation of AIE PSs.

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.

Bipolar Hemicyanine-Based Photodynamic Modulation of Type I Pathway for Efficient Sterilization and Real-Time Monitoring.

The development of photosensitizers with low oxygen dependence for generating type I ROS is in high demand to be able to treat pathogenic infections in hypoxic conditions. Here, we report a series of cationic bipolar hemicyanines (C3, C6, and C10) with alkyl linkers of varying lengths that are found to exclusively produce hydroxyl radicals and superoxide radicals with the aid of white light and that have different antibacterial abilities toward a variety of pathogens. Furthermore, hemicyanines could differentiate live from dead bacteria to track the status of pathogens in real time. It is expected that hemicyanines could be applied for combatting various microbial infections in hypoxia and real-time tracking.