Photo-Controllable Smart Hydrogels for Biomedical Application: A Review.

Nowadays, smart hydrogels are being widely studied by researchers because of their advantages such as simple preparation, stable performance, response to external stimuli, and easy control of response behavior. Photo-controllable smart hydrogels (PCHs) are a class of responsive hydrogels whose physical and chemical properties can be changed when stimulated by light at specific wavelengths. Since the light source is safe, clean, simple to operate, and easy to control, PCHs have broad application prospects in the biomedical field. Therefore, this review timely summarizes the latest progress in the PCHs field, with an emphasis on the design principles of typical PCHs and their multiple biomedical applications in tissue regeneration, tumor therapy, antibacterial therapy, diseases diagnosis and monitoring, etc. Meanwhile, the challenges and perspectives of widespread practical implementation of PCHs are presented in biomedical applications. This study hopes that PCHs will flourish in the biomedical field and this review will provide useful information for interested researchers.

Photocatalytic Antimicrobials: Principles, Design Strategies, and Applications.

Nowadays, the increasing emergence of antibiotic-resistant pathogenic microorganisms requires the search for alternative methods that do not cause drug resistance. Phototherapy strategies (PTs) based on the photoresponsive materials have become a new trend in the inactivation of pathogenic microorganisms due to their spatiotemporal controllability and negligible side effects. Among those phototherapy strategies, photocatalytic antimicrobial therapy (PCAT) has emerged as an effective and promising antimicrobial strategy in recent years. In the process of photocatalytic treatment, photocatalytic materials are excited by different wavelengths of lights to produce reactive oxygen species (ROS) or other toxic species for the killing of various pathogenic microbes, such as bacteria, viruses, fungi, parasites, and algae. Therefore, this review timely summarizes the latest progress in the PCAT field, with emphasis on the development of various photocatalytic antimicrobials (PCAMs), the underlying antimicrobial mechanisms, the design strategies, and the multiple practical antimicrobial applications in local infections therapy, personal protective equipment, water purification, antimicrobial coatings, wound dressings, food safety, antibacterial textiles, and air purification. Meanwhile, we also present the challenges and perspectives of widespread practical implementation of PCAT as antimicrobial therapeutics. We hope that as a result of this review, PCAT will flourish and become an effective weapon against pathogenic microorganisms and antibiotic resistance.

Developments on the Smart Hydrogel-Based Drug Delivery System for Oral Tumor Therapy.

At present, an oral tumor is usually treated by surgery combined with preoperative or postoperative radiotherapies and chemotherapies. However, traditional chemotherapies frequently result in substantial toxic side effects, including bone marrow suppression, malfunction of the liver and kidneys, and neurotoxicity. As a new local drug delivery system, the smart drug delivery system based on hydrogel can control drug release in time and space, and effectively alleviate or avoid these problems. Environmentally responsive hydrogels for smart drug delivery could be triggered by temperature, photoelectricity, enzyme, and pH. An overview of the most recent research on smart hydrogels and their controlled-release drug delivery systems for the treatment of oral cancer is given in this review. It is anticipated that the local drug release method and environment-responsive benefits of smart hydrogels will offer a novel technique for the low-toxicity and highly effective treatment of oral malignancy.

Engineering Single-Atom Active Sites on Covalent Organic Frameworks for Boosting CO2 Photoreduction.

Solar carbon dioxide (CO2) conversion is an emerging solution to meet the challenges of sustainable energy systems and environmental/climate concerns. However, the construction of isolated active sites not only influences catalytic activity but also limits the understanding of the structure-catalyst relationship of CO2 reduction. Herein, we develop a universal synthetic protocol to fabricate different single-atom metal sites (e.g., Fe, Co, Ni, Zn, Cu, Mn, and Ru) anchored on the triazine-based covalent organic framework (SAS/Tr-COF) backbone with the bridging structure of metal-nitrogen-chlorine for high-performance catalytic CO2 reduction. Remarkably, the as-synthesized Fe SAS/Tr-COF as a representative catalyst achieved an impressive CO generation rate as high as 980.3 µmol g-1 h-1 and a selectivity of 96.4%, over approximately 26 times higher than that of the pristine Tr-COF under visible light irradiation. From X-ray absorption fine structure analysis and density functional theory calculations, the superior photocatalytic performance is attributed to the synergic effect of atomically dispersed metal sites and Tr-COF host, decreasing the reaction energy barriers for the formation of *COOH intermediates and promoting CO2 adsorption and activation as well as CO desorption. This work not only affords rational design of state-of-the-art catalysts at the molecular level but also provides in-depth insights for efficient CO2 conversion.

Incorporating Boron into Niobic Acid Nanosheets Enables Generation of Multiple Reactive Oxygen Species for Superior Antibacterial Action.

Photocatalytic therapy is an alternative antibacterial pathway but most photocatalysts are limited by light absorption, charge transfer and insufficient production of reactive oxygen species (ROS). Herein, the authors utilize boron doped niobic acid nanosheets (B-HNbO3 NSs) as a superior photocatalytic antibacterial platform. The experimental results and density functional theory (DFT) confirm that superior photocatalytic therapy activity is mainly due to boron doping, which not only promotes the generation and separation of electrons and holes, but also enhances the adsorption of water and oxygen molecules on B-HNbO3 NSs. Consequently, multiple ROS including hydroxyl radicals (•OH), superoxide radicals (•O2- ), and singlet oxygen (1 O2 ) are generated under light irradiation, resulting in outstanding bacterial killing ability of B-HNbO3 NSs. Besides, oxygen is produced during the therapy process, thus alleviating the inflammatory response caused by hypoxia. Furthermore, molecular dynamics (MD) simulations verify that the nanosheet structure makes it possess strong electrostatic attraction for bacterial cell membranes, leading to physical insertion and damage to bacterial cells. Therefore, bactericidal rates for four types of bacteria are all more than 99%, proving its excellent and broad-spectrum antibacterial capacity. Moreover, B-HNbO3 NSs could be applied to treat biofilm-coated medical devices in vivo, suggesting its possibility in practical application.

Accelerated antibacterial red-carbon dots with photodynamic therapy against multidrug-resistant Acinetobacter baumannii.

The emergence of antibiotic resistance in bacteria is a major public-health issue. Synthesis of efficient antibiotic-free material is very important for fighting bacterial infection-related diseases. Herein, red-carbon dots (R-CDs) with a broad range of spectral absorption (350-700 nm) from organic bactericides or intermediates were synthesized through a solvothermal route. The prepared R-CDs not only had intrinsic antibacterial activities, but also could kill multidrug-resistant bacteria (multidrug-resistant Acinetobacter baumannii (MRAB) and multidrug-resistant Staphylococcus aureus (MRSA)) effectively by generating reactive oxygen species. Furthermore, R-CDs could eliminate and inhibit the formation of MRAB biofilms, while conferring few side effects on normal cells. A unique property of R-CDs was demonstrated upon in vivo treatment of antibiotic-sensitive MRAB-induced infected wounds. These data suggested that this novel R-CDs-based strategy might enable the design of next-generation agents to fight drug-resistant bacteria. Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s40843-021-1770-0 and is accessible for authorized users.

Organic Photo-antimicrobials: Principles, Molecule Design, and Applications.

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

A photo-sensitizable phage for multidrug-resistant Acinetobacter baumannii therapy and biofilm ablation.

Antibiotic abuse causes the emergence of bacterial resistance. Photodynamic antibacterial chemotherapy (PACT) has great potential to solve serious bacterial resistance, but it suffers from the inefficient generation of ROS and the lack of bacterial targeting ability. Herein, a unique cationic photosensitizer (NB) and bacteriophage (ABP)-based photodynamic antimicrobial agent (APNB) is developed for precise bacterial eradication and efficient biofilm ablation. Thanks to the structural modification of the NB photosensitizer with a sulfur atom, it displays excellent reactive oxygen species (ROS)-production ability. Moreover, specific binding to pathogenic microorganisms can be provided by bacteriophages. The developed APNB has multiple functions, including bacteria targeting, near-infrared fluorescence imaging and combination therapy (PACT and phage therapy). Both in vitro and in vivo experiments prove that APNB can efficiently treat A. baumannii infection. Particularly, the recovery from A. baumannii infection after APNB treatment is faster than that with ampicillin and polymyxin B in vivo. Furthermore, the strategy of combining bacteriophages and photosensitizers is employed to eradicate bacterial biofilms for the first time, and it shows the excellent biofilm ablation effect as expected. Thus, APNB has huge potential in fighting against multidrug-resistant bacteria and biofilm ablation in practice.

[Research progress on chemical constituents and their differences between sea buckthorn berries and leaves].

Sea buckthorn berries and leaves are two medicinal parts derived from the same primitive plant,mostly used as ethnic medicine,which have a long history in Mongolian and Tibetan. This paper reviews the studies on the chemical composition and differences between sea buckthorn berries and leaves. They have the same or similar composition and content of flavonoids,triterpenes,steroids,organic acids and volatile oils,also have some differences. The main differences are as follows: the flavonoids content in the sea buckthorn leaves is greater than that of the sea buckthorn berries,but the species of flavonoids in the berries are higher than leaves. The species and content of steroids and organic acids in the berries are higher than that of the leaves. The berries contain abundant volatile oil,and the leaves contain many phenolic compounds. Finally,the main problems and the prospect of the next research are put forward.

Fe-T1 Sensor Based on Coordination Chemistry for Sensitive and Versatile Bioanalysis.

The main challenge of paramagnetic ions-mediated magnetic sensors is their relatively low sensitivity. In this study, we observe the amplification of longitudinal relaxation time (T1) signal when Fe2+ transforms into Fe3+ followed by the coordination of potassium thiocyanate (KSCN) and develop a sensitive Fe-T1 sensor based on the coordination chemistry between KSCN and Fe3+ to amplify the T1 signal for detecting a series of targets, such as hydrogen peroxide, glucose, and antigen/antibody. We justify the practicability of our assay by successfully detecting tetracycline in milk samples and hepatitis C virus in clinical samples with satisfactory accuracy. This KSCN-mediated Fe-T1 sensor not only realizes biochemical analysis and immunoassay with higher sensitivity but also retains many advantages of paramagnetic ions-mediated magnetic sensors (good stability and straightforward operation), which holds great promise for the detection of a range of targets of interest in complex samples.

Peptide-Mediated Controllable Cross-Linking of Gold Nanoparticles for Immunoassays with Tunable Detection Range.

The colorimetric immunoassay based on gold nanoparticles (AuNPs) can hardly enable simultaneous detection of multiple biomarkers in vastly different concentrations (e.g., pg/mL-µg/mL) because of its narrow dynamic range. In this work, we demonstrate an immunoassay with tunable detection range by using peptide-mediated controlled aggregation of surface modification-free AuNPs. Alkaline phosphatase (ALP) removes the phosphate group of the peptide to yield a positively charged product, which triggers the aggregation of negatively charged AuNPs and the color change of the AuNPs solution from red to blue with naked-eye readout. We design and screen 20 kinds of phosphorylated peptides to obtain a broad and controllable detection range for ALP sensing and apply them for detecting multiple inflammatory biomarkers in clinical samples. Our assay realizes straightforward, multiplexed, and simultaneous detection of multiple clinical biomarkers with tunable detection range (from pg/mL to µg/mL) in the same run and holds great potential for chemical/biochemical analysis.

Cu-T1 Sensor for Versatile Analysis.

Conventional magnetic sensors usually employ Fe-based magnetic materials as signal probes. In this work, we find that Cu(II) is also a useful longitudinal relaxation time (T1) signal-based magnetic probe. We adopt bathocuproinedisulfonic acid disodium salt hydrate (BCS) to chelate Cu(I) and form a stable Cu(I)-BCS complex in aqueous solution and find the significant difference in the T1 value of water protons between Cu(II) aqueous solution and Cu(I)-BCS complex aqueous solution. Redox reaction can convert Cu(II) to Cu(I) followed by the complexation of BCS, which results in apparent change of T1 that can serve as magnetic signal readout, which is the basis of this Cu-T1 sensor. Many redox reactions between Cu(II) and Cu(I) allow this Cu-T1 sensor to not only realize "one-step mode" assay such as ascorbic acid, protein, and alkaline phosphatase but also enable "multi-step mode" immunoassay, such as biomacromolecules and small molecules. This Cu-T1 sensor employs Cu ion as signal readout, providing an alternative tool for biochemical analysis.

Small Molecular TGF-ß1-Inhibitor-Loaded Electrospun Fibrous Scaffolds for Preventing Hypertrophic Scars.

Hypertrophic scarring (HS) is a disorder that occurs during wound healing and seriously depresses the quality of human life. Scar-inhibiting scaffolds, though bringing promise to HS prevention, face problems such as the incompatibility of the scaffold materials and the instability of bioactive molecules. Herein, we present a TGF-ß1-inhibitor-doped poly(ε-caprolactone) (PCL)/gelatin (PG) coelectrospun nanofibrous scaffold (PGT) for HS prevention during wound healing. The appropriate ratio of PCL to gelatin can avoid individual defects of the two materials and achieve an optimized mechanical property and biocompatibility. The TGF-ß1 inhibitor (SB-525334) is a small molecule and is highly stable during electrospinning and drug release processes. The PGT effectively inhibits fibroblast (the major cell type contributing to scar formation) proliferation in vitro and successfully prevents HS formation during the healing of full-thickness model wounds on rabbit ear. Our strategy offers an excellent solution for potential large-scale production of scaffolds for clinical HS prevention.

Bioorthogonal Reaction-Mediated ELISA Using Peroxide Test Strip as Signal Readout for Point-of-Care Testing.

This work demonstrates a highly sensitive peroxide test strip (PTS)-based enzyme-linked immunosorbent assay (ELISA) for both qualitative and quantitative detection of drugs of abuse (morphine) and disease biomarkers (interleukin-6 and HIV-1 capsid antigen p24). This color-based PTS is a commercially available product with advantages of low cost, easy operation, and portability, and it is an ideal signal readout strategy in ELISA to simplify the immunoassay procedures and enable point-of-care testing (POCT). In addition, we introduce the bioorthogonal reaction that can effectively amplify the signal by controlling the cycles of bioorthogonal reaction to achieve the desirable sensitivity depending on different analytes. The limit of detection is 0.2 ng/mL for morphine, 3.98 pg/mL for interleukin-6, and 11.6 pg/mL for detection of HIV-capsid antigen (p24). This PTS-ELISA applies to both the qualitative and quantitative detection of IL-6 and p24 in clinical serum samples with good accuracy, which provides a promising tool for the POCT in clinical diagnosis.

Pharmaceutical Intermediate-Modified Gold Nanoparticles: Against Multidrug-Resistant Bacteria and Wound-Healing Application via an Electrospun Scaffold.

Remedying a multidrug-resistant (MDR) bacteria wound infection is a major challenge due to the inability of conventional antibiotics to treat such infections against MDR bacteria. Thus, developing wound dressings for wound care, particularly against MDR bacteria, is in huge demand. Here, we present a strategy in designing wound dressings: we use a small molecule (6-aminopenicillanic acid, APA)-coated gold nanoparticles (AuNPs) to inhibit MDR bacteria. We dope the AuNPs into electrospun fibers of poly(ε-caprolactone) (PCL)/gelatin to yield materials that guard against wound infection by MDR bacteria. We systematically evaluate the bactericidal activity of the AuNPs and wound-healing capability via the electrospun scaffold. APA-modified AuNPs (Au_APA) exhibit remarkable antibacterial activity even when confronted with MDR bacteria. Meanwhile, Au_APA has outstanding biocompatibility. Moreover, an in vivo bacteria-infected wound-healing experiment indicates that it has a striking ability to remedy a MDR bacteria wound infection. This wound scaffold can assist the wound care for bacterial infections.

"One-for-All"-Type, Biodegradable Prussian Blue/Manganese Dioxide Hybrid Nanocrystal for Trimodal Imaging-Guided Photothermal Therapy and Oxygen Regulation of Breast Cancer.

Multimodal imaging-guided diagnosis and therapy has been highlighted in the area of theranostic nanomaterials. To provide more suitable theranostic candidates, Prussian blue (PB)/manganese dioxide (MnO2) hybrid nanoparticles (PBMn) smaller than 50 nm are prepared by a one-pot method. MnO2, which is reduced from KMnO4, not only controls the particle size, the optical properties, and the transverse relaxation rate (r2) of PB but also enhances the catalysis efficacy of PB to H2O2 for oxygen generation. PBMn can serve as a photoacoustic imaging (PAI) and longitudinal relaxation (T1) mode magnetic resonance imaging contrast agent (14 times and 1.8 times of the saline-treated group, respectively). Injection of PBMn can regulate the oxygen partial pressure of the tumor tissue from 2.1 ± 0.2 to 9.3 ± 0.4 kPa and rearrange the ratio of oxygenated hemoglobin and deoxygenate hemoglobin inside the tumor, which favor the enhancement of the diamagnetic T2-weighted imaging (T2WI) signal intensity (two times that of the saline-treated group). Furthermore, PBMn-mediated PTT can efficiently inhibit the growth of the MCF-7 tumor in vitro and in vivo. PBMn can serve as a PAI/T1/T2 trimodal contrast agent and in imaging-guided PTT, as well as in the oxygen regulation of the exografted breast cancer.

Polymer hybrid magnetic nanocapsules encapsulating IR820 and PTX for external magnetic field-guided tumor targeting and multifunctional theranostics.

Developing multifunctional nanoparticle-based theranostic systems for personalized cancer diagnosis and treatment is highly desirable. Herein, a magnetic targeting theranostic nanocapsule (NC-SPIOs-IR820-PTX) was fabricated by hierarchically assembling superparamagnetic iron oxide nanoparticles (SPIOs), cyanine dye (IR820) and chemotherapeutic compound of paclitaxel (PTX) with poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA). The nanocapsules exhibited high stability and biocompatibility both in vitro and in vivo. The nanocomposites maintained their morphology in the cellular uptake and showed efficient tumoricidal activity. Most importantly, the external magnetic field could remotely control the nanocapsules and guide them to target tumors for magnetic resonance imaging (MRI)/near-infrared (NIR) fluorescence imaging. The synergistic therapeutic effects of NC-SPIOs-IR820-PTX with extra-magnetic field-induced tumor targeting ability have enhanced the co-therapy of photo-chemotherapy, resulting in significant tumor inhibition effects. Therefore, NC-SPIOs-IR820-PTX theranostics could be applied for magnetic field guided tumor targeting as well as multimodal MRI/NIR imaging, and imaging-guided combined therapy.

One-step multiplexed detection of foodborne pathogens: Combining a quantum dot-mediated reverse assaying strategy and magnetic separation.

A rapid and multiplexed immunosensor was developed based on a quantum dot (QD)-reverse assaying strategy (RAS) and immuno-magnetic beads (IMBs) for one-step and simultaneous detection of Escherichia coli O157: H7 and Salmonella. In a conventional QD-based immunosensor, the fluorescence signal of the "IMBs-target-QD" immunoconjugate is directly used as the assaying readout. However, the fluorescence signal is affected by IMBs due to light scattering and the "IMBs-target-QD" immunoconjugate needs multiple washing and re-suspension steps. To address these problems, we use the surplus QD-antibody conjugate as signal readout in the RAS, which prevents interference from the IMBs, increases the fluorescence signal, and avoids complex operations. Compared with conventional QD-based immunosensor, the sensitivity of QD-RSA immunosensor for detection of Escherichia coli O157: H7 has been improved fifty-fold, and whole analysis procedure can be finished within 1h. Therefore, this RSA strategy is promising for improving the performance of QD-based immunosensors and could greatly broaden their applications.