No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Phospholipid membrane-protected photoelectrochemical chip: A specific test-to-treat platform for bacteria secreting pore-forming toxins with phosphatidylcholine receptor
... However, red fluorescence emissions from MB in BIMs became gradually stronger along with the incubation time. PFTs are the largest class of protein toxins and produced by various pathogenic bacteria including S. aureus and P. aeruginosa, [41] and ICB-derived PFTs and lipase triggered the release of nMB from NPs after endocytosis into BIMs. nMB small molecules could freely diffused into or be actively pumped into both Gram-positive and negative bacteria, [28] followed by transformation into MB for turn-on fluorescence in response to intrabacterial NTR. ...
... The generation of ROS in BIMs after mSC-nMB@BM/US treatment was examined by using 2,7-dichlorofluorescin diacetate (DCFH-DA) probes, which were rapidly oxidized by ROS to generate DCFH molecule with strong green fluorescence emissions. [41] To observe the location of ROS production and DCFH fluorescence (green), bacteria were labelled with Did (red), which was a lipophilic dye and could provide a stable and specific labeling of the membrane and lipids. [42] Did-labelled bacteria were internalized by Mø to established fluorescently labeled ICBs, and Figure 5c displays the emerged images with DAPI-stained nuclei at high magnifications. ...
Intracellular bacterial (ICB) infection is one of the most life‐threatening cases of drug resistance, and photodynamic therapy (PDT) is challenged by limited light penetration into tissues and unspecific toxicity to host cells. Herein, theranostic nanoparticles (NPs) are developed to facilitate on‐demand activation of photosensitizers inside ICBs and persistent PDT of deep‐tissue ICB infections. Mechanoluminescent SrAl2O4:Eu²⁺ and persistence luminescent CaS:Eu²⁺ are sequentially deposited on mesoporous silica to prepare mSC, followed by encapsulation by bacterial membranes with loaded nitroreductase (NTR)‐activatable methylene blue (nMB) to obtain mSC‐nMB@BM NPs. The fluorescence quenching of nMB with mSC offers few cytotoxicities even under ultrasonication, and bacterial membrane coatings mediate the specific NP internalization into ICB‐infected macrophages. Bacterial pore‐forming toxins trigger nMB release from NPs, and intrabacterial NTR rejuvenates methylene blue probes from nMB for real‐time imaging of ICB infections. Ultrasonication of NPs continuously excites the rejuvenated methylene blue to generate reactive oxidative species and reduce viable ICBs by 3.54 log magnitude folds. NP treatment on ICB‐infected mice exhibits full survival and restores viscera functions without any pathological abnormality. Therefore, this concise NP design demonstrates capabilities of bacterial membrane‐mediated specific internalization, bacterial toxin‐triggered release and intrabacterial NTR‐rejuvenation of fluorescent probes, and persistent internal light‐illumination for ICB theranostics.
Perovskite quantum dots (PQDs) have attracted much attention in the field of photoelectrochemical (PEC) sensors owing to their superb optical properties and efficient charge transport, but the inherent poor stability severely hinders their PEC applications. Herein, hydrolysis‐resistant CsPbBr3/reduced graphene oxide nanoscrolls (CsPbBr3/rGO NSs) are obtained by solvent‐assisted self‐rolling process toward water‐stable PEC sensors. CsPbBr3 QDs embedded in rGO nanosheets can be prevented from water since the multilayer rGO shell layers, which maintains excellent optical properties. On account of strong interfacial interactions, rGO nanosheets are crimped spontaneously with CsPbBr3 QDs, which offer access to superb structural and long‐term storage stability. Moreover, appropriate band alignment and ultrafast interfacial carrier transfer enable CsPbBr3/rGO NSs to exhibit greatly enhanced anode photocurrent response for subsequent PEC sensing. As a demonstration, the molecular imprinted PEC sensors for two kinds of mycotoxins (aflatoxin B1 or ochratoxin A) presents an ultra‐high sensitivity and good anti‐interference ability. Significantly, this work provides an inspirable and convenient route for hydrolysis‐resistant PQDs‐based optoelectronic and photoelectrocatalytic applications in aqueous ambience.
Background
Phellinus linteus (PL), which is a typical medicinal fungus, has been shown to have antitumor and anti-inflammatory activities. However, studies on the effect of anti-photoaging are limited. Studies have shown that exosome-like nanovesicles are functional components of many medicinal plants, and miRNAs in exosome-like nanovesicles play a cross-kingdom regulatory role. At present, research on fungi exosome-like nanovesicles (FELNVs) is few.
Results
We systematically evaluated the anti-aging effects of PL. FELNVs of PL were isolated, and the functional molecular mechanisms were evaluated. The results of volunteer testing showed that PL had anti-aging activity. The results of component analysis showed that FELNVs were the important components of PL function. FELNVs are nanoparticles (100–260 nm) with a double shell structure. Molecular mechanism research results showed that miR-CM1 in FELNVs could inhibit Mical2 expression in HaCaT cells through cross-kingdom regulation, thereby promoting COL1A2 expression; inhibiting MMP1 expression in skin cells; decreasing the levels of ROS, MDA, and SA-β-Gal; and increasing SOD activity induced by ultraviolet (UV) rays. The above results indicated that miR-CM1 derived from PL inhibited the expression of Mical2 through cross-kingdom regulation and inhibited UV-induced skin aging.
Conclusion
miR-CM1 plays an anti-aging role by inhibiting the expression of Mical2 in human skin cells through cross-species regulation.
Graphical abstract
Photoredox catalysis has emerged as a robust tool for chemical synthesis. However, it remains challenging to implement photoredox catalysis under physiological conditions due to the complex microenvironment and the quenching of photocatalyst by biologically relevant molecules such as oxygen. Here, we report that UV‐absorbing N,N′‐dinitroso‐1,4‐phenylenediamine derivatives can be selectively activated by fac‐Ir(ppy)3 photocatalyst within micellar nanoparticles under visible light irradiation (e.g., 500 nm) through photoredox catalysis in aerated aqueous solutions to form quinonediimine (QDI) residues with concomitant release of NO. Notably, the formation of QDI derivatives can actively scavenge the reactive oxygen species generated by fac‐Ir(ppy)3, thus avoiding oxygen quenching of the photocatalyst. Further, we exemplify that the oxygen‐tolerant photoredox catalysis‐mediated NO release can not only kill planktonic bacteria in vitro but also efficiently treat MRSA infections in vivo.
Chronic exposure to inorganic arsenic is a major environmental public health issue worldwide affecting more than 220 million of people. Previous studies have shown the correlation between arsenic poisoning and cellular senescence; however, knowledge regarding the mechanism and effective prevention measures has not been fully studied. First, the associations among the ERK/CEBPB signaling pathway, oxidative stress, and arsenic-induced skin cell senescence were confirmed using the HaCaT cell model. In the arsenic-exposed group, the relative mRNA and protein expressions of ERK/CEBPB signaling pathway indicators (ERK1, ERK2, and CEBPB), cell cycle-related genes (p21, p16INK4a), and the secretion of SASP (IL-1α, IL-6, IL-8, TGF-β1, MMP-1, MMP-3, EGF, and VEGF) and the lipid peroxidation product (MDA) were significantly increased in cells (P
The detection of Rhamnolipid virulence factor produced by Pseudomonas aeruginosa involved in nosocomial infections is reported by using the redox liposome single impact electrochemistry. Redox liposomes based on 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine as a pure phospholipid and potassium ferrocyanide as an encapsulated redox content are designed for using the interaction of the target toxin with the lipid membrane as a sensing strategy. The electrochemical sensing principle is based on the weakening of the liposomes lipid membrane upon interaction with Rhamnolipid toxin which leads upon impact at an ultramicroelectrode to the breakdown of the liposomes and the release/electrolysis of its encapsulated redox probe. We present as a proof of concept the sensitive and fast sensing of a submicromolar concentration of Rhamnolipid which is detected after less than 30 minutes of incubation with the liposomes, by the appearing of current spikes in the chronoamperometry measurement.
Nitric oxide (NO) serves as a key regulator of many physiological processes and as a potent therapeutic agent. The local delivery of NO is important to achieve target therapeutic outcomes due to the toxicity of NO at high concentrations. Although light stimulus represents a non‐invasive tool with spatiotemporal precision to mediate NO release, many photoresponsive NO‐releasing molecules can only respond to ultraviolet (UV) or near‐UV visible light with low penetration and high phototoxicity. We report that coumarin‐based NO donors with maximal absorbances at 328 nm can be activated under (deep) red‐light (630 or 700 nm) irradiation in the presence of palladium(II) tetraphenyltetrabenzoporphyrin, enabling stoichiometric and self‐reporting NO release with a photolysis quantum yield of 8 % via photoredox catalysis. This NO‐releasing platform with ciprofloxacin loading can eradicate Pseudomonas aeruginosa biofilm in vitro and treat cutaneous abscesses in vivo.
Single atom (SA) catalysis, over the last 10 years, has become a forefront in heterogeneous catalysis, electrocatalysis, and most recently also in photocatalysis. Most crucial when engineering a SA catalyst/support system is the creation of defined anchoring points on the support surface to stabilize reactive SA sites. Here, a so far unexplored but evidently very effective approach to trap and stabilize SAs on a broadly used photocatalyst platform is introduced. In self-organized anodic TiO2 nanotubes, a high degree of stress is incorporated in the amorphous oxide during nanotube growth. During crystallization (by thermal annealing), this leads to a high density of Ti³⁺-Ov surface defects that are hardly present in other common titania nanostructures (as nanoparticles). These defects are highly effective for SA iridium trapping. Thus a SA-Ir photocatalyst with a higher photocatalytic activity than for any classic co-catalyst arrangement on the semiconductive substrate is obtained. Hence, a tool for SA trapping on titania-based back-contacted platforms is provided for wide application in electrochemistry and photoelectrochemistry. Moreover, it is shown that stably trapped SAs provide virtually all photocatalytic reactivity, with turnover frequencies in the order of 4 × 10⁶ h⁻¹ in spite of representing only a small fraction of the initially loaded SAs.
Streptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1.
Extracellular vesicles are membranous structures shed by almost every living cell. Bacterial gram-negative outer membrane vesicles (OMVs) and gram-positive membrane vesicles (MVs) play important roles in adaptation to the surrounding environment, cellular components' exchange, transfer of antigens and virulence factors, and infection propagation. Streptococcus pneumoniae is considered one of the priority pathogens, with a global health impact due to the increase in infection burden and growing antibiotic resistance. We isolated MVs produced from the S. pneumoniae reference strain (R6) and purified them via size exclusion chromatography (SEC) to remove soluble protein impurities. We characterized the isolated MVs by nanoparticle tracking analysis (NTA) and measured their particle size distribution and concentration. Isolated MVs showed a mean particle size range of 130–160 nm and a particle yield of around 1012 particles per milliliter. Cryogenic transmission electron microscopy (cryo-TEM) images revealed a very heterogeneous nature of isolated MVs with a broad size range and various morphologies, arrangements, and contents. We incubated streptococcal MVs with several mammalian somatic cells, namely, human lung epithelial A549 and human keratinocytes HaCaT cell lines, and immune cells including differentiated macrophage-like dTHP-1 and murine dendritic DC2.4 cell lines. All cell lines displayed excellent viability profile and negligible cytotoxicity after 24-h incubation with MVs at concentrations reaching 10^6 MVs per cell (somatic cells) and 10^5 MVs per cell (immune cells). We evaluated the uptake of fluorescently labeled MVs into these four cell lines, using flow cytometry and confocal microscopy. Dendritic cells demonstrated prompt uptake after 30-min incubation, whereas other cell lines showed increasing uptake after 2-h incubation and almost complete colocalization/internalization of MVs after only 4-h incubation. We assessed the influence of streptococcal MVs on antigen-presenting cells, e.g., dendritic cells, using enzyme-linked immunosorbent assay (ELISA) and observed enhanced release of tumor necrosis factor (TNF)-α, a slight increase of interleukin (IL)-10 secretion, and no detectable effect on IL-12. Our study provides a better understanding of gram-positive streptococcal MVs and shows their potential to elicit a protective immune response. Therefore, they could offer an innovative avenue for safe and effective cell-free vaccination against pneumococcal infections.
The use of an endogenous stimulus instead of external trigger has an advantage for targeted and controlled release in drug delivery. Here, we report on cascade nanoreactors for bacterial toxin-triggered antibiotic release by wrapping calcium peroxide (CaO2) and antibiotic in a eutectic mixture of two fatty acids and a liposome coating. When encountering pathogenic bacteria in vivo these nanoreactors capture the toxins, without compromising their structural integrity, and the toxins form pores. Water enters the nanoreactors through the pores to react with CaO2 and produce hydrogen peroxide which decomposes to oxygen and drives antibiotic release. The bound toxins reduce the toxicity and also stimulate the body’s immune response. This works to improve the therapeutic effect in bacterially infected mice. This strategy provides a Domino Effect approach for treating infections caused by bacteria that secrete pore-forming toxins.
Simultaneous imaging and treatment of infections remains a major challenge, with most current approaches being effective against only one specific group of bacteria or not being useful for diagnosis. Here we develop multifunctional nanoagents that can potentially be used for imaging and treatment of infections caused by diverse bacterial pathogens. The nanoagents are made of fluorescent silicon nanoparticles (SiNPs) functionalized with a glucose polymer (e.g., poly[4-O-(α-D-glucopyranosyl)-D-glucopyranose]) and loaded with chlorin e6 (Ce6). They are rapidly internalized into Gram-negative and Gram-positive bacteria by a mechanism dependent on an ATP-binding cassette (ABC) transporter pathway. The nanoagents can be used for imaging bacteria by tracking the green fluorescence of SiNPs and the red fluorescence of Ce6, allowing in vivo detection of as few as 105 colony-forming units. The nanoagents exhibit in vivo photodynamic antibacterial efficiencies of 98% against Staphylococcus aureus and 96% against Pseudomonas aeruginosa under 660 nm irradiation.
Titania is one of the key materials used in 1D, 2D, and 3D nanostructures as electron transport media in energy conversion devices. In the present study, it is shown that the electronic properties of TiO2 nanotubes can be drastically improved by inducing a nanotwinned grain structure in the nanotube wall. This structure can be exclusively induced for “single‐walled” nanotubes with a high‐temperature treatment in pure oxygen atmospheres. Nanotubes with a twinned grain structure within the tube wall show a strongly enhanced conductivity and photogenerated charge transport compared to classic nanotubes. This remarkable improvement is exemplified in the electronic properties by using nanotwinned TiO2 nanotubes in dye‐sensitized solar cells where a significant increase in efficiency of up to 10.2% is achieved. Nanotwinned grain structures in the TiO2 nanotube walls can be induced for “single‐walled” nanotubes via high‐temperature treatment in pure oxygen atmosphere. Such twinned nanotubes show a strongly enhanced conductivity and photogenerated charge transport compared to classical nanotubes and can lead to efficiencies of up to 10.23% in dye‐sensitized solar cells.
The design and fabrication of bio‐photoelectrodes that simultaneously possess rapid charge and gas‐phase mass transport abilities are highly desirable for the development of high‐performance bio‐photoelectrochemical assay systems. Here, a solid–liquid–air triphase bio‐photoelectrode is demonstrated by immobilizing glucose oxidase, a model redox active enzyme, onto 1D single crystalline TiO2 nanowire arrays grown upon a superhydrophobic carbon textile substrate. Based on this triphase bio‐photoelectrode system, oxygen can be directly and constantly supplied from the air phase to sustain enzymatic reactions, leading to much enhanced oxidase kinetics. Further, the photogenerated electrons can transport rapidly and be efficiently collected along the nanowire arrays. The bio‐photoelectrochemical assay system demonstrates a significant wide detection range, high sensitivity, and selectivity as well as a low detection limit. The design principle is generally applicable to the fabrication of other triphase bio‐photoelectrodes, which offers an excellent opportunity for significant advances in environmental analysis and clinical diagnosis.
Photocatalytic water splitting requires separation of the mixed H2 and O2 products and is often hampered by the sluggish O2-producing half reaction. Herein, we report, for the first time, a novel approach to address these issues by coupling the H2-producing half reaction with value-added benzylamine oxidation reaction using metal-organic framework (MOF) composites. Upon MOF photoexcitation, the electrons rapidly reduce the protons to generate H2 and the holes promote considerable benzylamine oxidation to N-benzylbenzaldimine with high selectivity. Further experimental characterizations and theoretical calculation reveal that the highly conjugated s-triazine strut in the MOF structure is crucial to the efficient charge separation and excellent photocatalytic activity.
In present work, we report on the use of organized TiO2 nanotube layers with a regular intertube spacing for the growth of highly defined α-Fe2O3 nano-needles in the interspace. These α-Fe2O3 decorated TiO2 NTs are then explored for Li-ion battery applications and compared to classic close-packed NTs that are both decorated with various amounts of nanoscale α-Fe2O3. We show that nanotubes with tube-to-tube spacing allow a uniform decoration of individual nanotubes with regular arrangements of hematite nano-needles. The tube spacing also facilitates the electrolyte penetration as well as yields better ion diffusion. While bare close-packed NTs show higher capacitance, e.g., 71 µAh cm-2 than bare spaced NTs with e.g., 54 µAh cm-2, the hierarchical decoration with secondary metal oxide, α-Fe2O3, remarkably enhances the Li-ion battery performance. Namely, spaced nanotubes with α-Fe2O3 decoration have an areal capacitance of 477 µAh cm-2, i.e., show up to nearly ~8 times higher capacitance. However, the areal capacitance of close-packed NTs with α-Fe2O3 decoration saturates at 208 µAh cm-2, i.e., is limited to ~3 times increase.
Factors governing the photoelectrochemical output of photosynthetic microorganisms are poorly understood, which can lead to energy losses through inefficient electron transfer (ET) processes. Here, we systematically compare the photoe-lectrochemistry of photosystem II (PSII) protein-films to cyano-bacteria biofilms to derive: (i) the losses in light-to-charge con-version efficiencies, (ii) gains in photocatalytic longevity, and (iii) insights into the ET mechanism at the biofilm interface. This study was enabled by the use of hierarchically structured elec-trodes, which could be tailored for high/stable loadings of PSII core complexes and Synechocystis sp. PCC 6803 cells. The pho-tocurrent densities generated by the biofilm were two orders of magnitude lower than those of the protein-film. This was attribut-ed to a lower photocatalyst loading since the rate of electron ex-traction from PSII in vitro is only double that of PSII in vivo. On the other hand, the biofilm exhibited much greater longevity (>5 days) than the protein-film (<6 h), with turnover numbers surpas-sing those of the protein-film after 2 days. The mechanism of the electrogenesis was revealed to involve an intracellular redox me-diator, which is released during light irradiation.
Herein is developed a ternary heterostructured catalyst, based on a periodic array of 1D TiN nanotubes, with a TiO2 nanoparticulate intermediate layer and a In2O3-x(OH)
y
nanoparticulate shell for improved performance in the photocatalytic reverse water gas shift reaction. It is demonstrated that the ordering of the three components in the heterostructure sensitively determine its activity in CO2 photocatalysis. Specifically, TiN nanotubes not only provide a photothermal driving force for the photocatalytic reaction, owing to their strong optical absorption properties, but they also serve as a crucial scaffold for minimizing the required quantity of In2O3-x(OH)
y
nanoparticles, leading to an enhanced CO production rate. Simultaneously, the TiO2 nanoparticle layer supplies photogenerated electrons and holes that are transferred to active sites on In2O3-x(OH)
y
nanoparticles and participate in the reactions occurring at the catalyst surface.
Skin infections are major threats to human health, causing ∼500 incidences per 10 000 person-year. In patients with diabetes mellitus, particularly, skin infections are often accompanied by a slow healing process, amputation, and even death. Timely diagnosis of skin infection strains and on-site therapy are vital in human health and safety. Herein, a double-layered "test-to-treat" pad is developed for the visual monitoring and selective treatment of drug-sensitive (DS)/drug-resistant (DR) bacterial infections. The inner layer (using carrageenan hydrogel as a scaffold) is loaded with bacteria indicators and an acid-responsive drug (Fe-carbenicillin frameworks) for infection detection and DS bacteria inactivation. The outer layer is a mechanoluminescence material (ML, CaZnOS:Mn2+) and visible-light responsive photocatalyst (Pt@TiO2) incorporated elastic polydimethylsiloxane (PDMS). On the basis of the colorimetric sensing result (yellow for DS-bacterial infection and red for DR-bacterial infection), a suitable antibacterial strategy is guided and then performed. Two available bactericidal routes provided by double pad layers reflect the advantage. The controllable and effective killing of DR bacteria is realized by in situ generated reactive oxygen species (ROSs) from the combination of Pt@TiO2 and ML under mechanical force, avoiding physical light sources and alleviating off-target side effects of ROS in biomedical therapy. As a proof-of-concept, the "test-to-treat" pad is applied as a wearable wound dressing for sensing and selectively dealing with DS/DR bacterial infections in vitro and in vivo. This multifunctional design effectively reduces antibiotic abuse and accelerates wound healing, providing an innovative and promising Band-Aid strategy in point-of-care diagnosis and therapy.
Cardiac troponin I (cTnI) is an extremely sensitive biomarker for early indication of acute myocardial infarction (AMI). However, it still remains a tough challenge for many newly developed cTnI biosensors to achieve superior sensing performance including high sensitivity, rapid detection, and resistance to interference in clinical serum samples. Herein, a novel photocathodic immunosensor toward cTnI sensing has been successfully developed by designing a unique S-scheme heterojunction based on the porphyrin-based covalent organic frameworks (p-COFs) and p-type silicon nanowire arrays (p-SiNWs). In the novel heterojunction, the p-SiNWs are employed as the photocathode platform to acquire a strong photocurrent response. The in situ-grown p-COFs can accelerate the spatial migration rate of charge carriers by forming proper band alignment with the p-SiNWs. The crystalline π-conjugated network of p-COFs with abundant amino groups also promotes the electron transfer and anti-cTnI immobilizing process. The developed photocathodic immunosensor demonstrates a broad detection range of 5 pg/mL-10 ng/mL and a low limit of detection (LOD) of 1.36 pg/mL in clinical serum samples. Besides, the PEC sensor owns several advantages including good stability and superior anti-interference ability. By comparing our results with that of the commercial ELISA method, the relative deviations range from 0.06 to 0.18% (n = 3), and the recovery rates range from 95.4 to 109.5%. This work displays a novel strategy to design efficient and stable PEC sensing platforms for cTnI detection in real-life serums and provides guidance in future clinical diagnosis.
Magnesium ion batteries (MIBs) attracted much attention in recently years due to the advantages of high theoretical capacity and low cost. However, the strong polarization effect of Mg²⁺ cause slow diffusion rate, hindering the development of MIBs. Herein, we designed and synthesized a binder-free polyaniline array/carbon cloth (PANI/CC) as cathode for MIBs. Given the benefit of improved electrical conductivity and alleviated agglomeration, the cathode exhibits enhanced electrochemical performance compared with the pure polyaniline cathode in MIBs. The PANI/CC cathode displays the highest specific capacity of 219 mA h g⁻¹ at 200 mA g⁻¹ and the capacity retention of 97.25% after over 1500 cycles at 1 A g⁻¹. Then, the reversible redox transformation between quinone rings and benzene rings during charging and discharging process was demonstrated by the ex-situ X-ray photoelectron spectroscopy (XPS) and ex-situ Raman spectra. In addition, PANI/CC shows an initial capacity of 75 mA h g⁻¹ at 50 mA g⁻¹ in PANI/CC //Mg(TFSI)2// MNTO full cell. Our work demonstrates that PANI/CC is a promising cathode for MIBs, which may offer new insight for the development for high-performance MIBs.
Infectious diseases caused by bacteria are a global threat to the human health. Here, we propose a solvent “irrigation” technique to endow TiO2 nanotubes (NTs) to precisely modify with functional nanomaterials, and apply them in constructing a near-infrared (NIR) light controlled drug-delivery system for rapid necrosis of bacteria. In this design, the NIR stimuli-responsive functional shell is located on the external tube wall of TiO2 NT; the internal tube wall offers sufficient binding sites for drug loading. Using kanamycin as a model drug, we demonstrate that the reactive oxygen species generated in photocatalysis not only controllably release the loaded drug by scissoring the linked chains, but also effectively compromise bacteria membrane integrity by damaging the cell wall. Benefiting from the damages, antibiotics rapidly enter the bacteria and reach ≥99.9% reduction in Escherichia coli colony within only 2 h. Importantly, such a covalently conjugation-based delivery system can efficiently relieve radical-induced inflammation and cytotoxicity. This study provides an innovative design strategy for engineering delivery systems with tailorable components, enduring stimuli-response by multiple triggers.
Recently evidence linking the effects of fine-dust (FD) on skin inflammation is exaggerating. Fucoidan derived from brown algae has great potential for ameliorating oxidative stress and inflammation. Herein, a fucoidan fraction (SHC4-6) was purified from an enzymatic (Celluclast) extract of an invasive seaweed, Sargassum horneri following gradient ethanol precipitation and anion exchange chromatography. Effectiveness of SHC4-6 in ameliorating FD (from Beijing, China)-induced inflammatory responses in HaCaT keratinocytes and recovery of skin barrier dysfunction was evaluated. SHC4-6 was comprising of sulfated mannofucans with their molecular weights distributed around 45 kDa. SHC4-6 dose-dependently lowered ROS levels in FD-induced HaCaT keratinocytes, ameliorating viability at 50 μg mL⁻¹. SHC4–6 downregulated inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, -5, -6, -8, -13, interferon-γ, and chemokines, macrophage-derived chemokine, eotaxin, and thymus and activation regulated chemokine by inhibiting mitogen-activated protein kinase and nuclear factor-κB pathways. SHC4–6 treatment ameliorated key tight junction proteins and skin hydration factors, depicting the effects of fucoidan in reducing FD-induced inflammation and skin barrier deterioration. With further studies in place, SHC4-6 could be used as an ingredient for developing cosmetics to relieve FD-induced skin inflammation.
Capture, analysis, and inactivation of circulating tumor cells (CTCs) have emerged as the important issues for the early diagnosis and therapy of cancer. In this study, an all-in-one sensing device was developed by integrating magnetic metal-organic framework (magMOF) nanoparticles (NPs) and TiO2 nanotube arrays (TiNTs). The magMOF NPs are composed of a magnetic Fe3O4 core and a MIL-100(Fe) shell, which is loaded with glucose oxidase (GOD) and provides an intensive starvation therapy by catalyzing the consumption of cellular nutrients, thus accelerating the generation of intracellular iron ions by MIL-100(Fe) dissolving. Importantly, these iron ions not only lead to an intensive Fenton-like reaction, but also establish an excellent correlation of electrochemical inten-sities with cancer cell numbers. Owing to the intracellular magMOF NPs, the CTCs were magnetically collected onto TiNTs. The exogenous •OH radicals generated by TiNTs photocatalysis trigger iron ions to rapidly release out and subsequently detected via differential pulse voltammetry using TiNTs as the electrode. An excellent correlation of DPV intensities with CTC numbers is ob-tained from 2 to 5000 cell mL-1. This nanoplatform not only paves a way to combine starvation therapy agents with Fenton-like reaction for chemodynamic therapy, but also open up new insights into the construction of an all-in-one chips for CTC capture and diagnosis.
This review focusses on unique material modification and signal amplification strategies reported in developing photoelectrochemical (PEC) biosensors with utmost sensitivity and selectivity. These successes have partly been achieved by applying photoactive materials that significantly circumvent major limitations including poor absorption of visible light, severe aggregation of nanostructures, easy charge recombination and low conductivity. In addition, several signal enhancement techniques were also demonstrated to have effectively improved the detection performance of PEC biosensors. Accordingly, we have begun this review with a systematic introduction of the concept, working principle, and characteristics of PEC biosensors. This was followed by a discussion of a range of material modification techniques, including quantum dot modification, metal/non-metal ion doping, formation of heterojunctions and Z-scheme composites, used in construction of PEC biosensors. Various signal amplification strategies including quantum dot sensitisation, application of electron donors, energy transfer effect, steric hindrances of biomolecules, and exfoliation of biomolecules from sensing surfaces are also presented in this review. Wherever possible, we have referred to relevant examples to explain and illustrate the corresponding working mechanism and effectiveness of the nanomaterials. Therefore, this review is aimed at providing an overall view on the current trend in material modification and signal amplification strategies for PEC biosensor development, which will aid in stimulating ideas for future progress in this field.
Burn is the immense public health issue globally. Low and middle income countries face extensive deaths owing to burn injuries. Availability of conventional therapies for burns has always been painful for patients as well as expensive for our health system. Pharmaceutical experts are still searching reliable, cheap, safe and effective treatment options for burn injuries. Fusidic acid is an antibiotic of choice for the management of burns. However, fusidic acid is encountering several pharmaceutical and clinical challenges like poor skin permeability and growing drug resistance against burn wound microbes like Methicillin resistant Staphylococcus aureus (MRSA). Therefore, an effort has been made to present a concise review about molecular pathway followed by fusidic acid in the treatment of burn wound infection in addition to associated pros and cons. Furthermore, we have also summarized chitosan and phospholipid based topical dermal delivery systems customized by our team for the delivery of fusidic acid in burn wound infections on case-to-case basis. However, every coin has two sides. We recommend the integration of in-silico docking techniques with natural biomacromolecules while designing stable, patient friendly and cost effective topical drug delivery systems of fusidic acid for the management of burn wound infection as future opportunities.
Photoelectrochemical sensing has developed rapidly in the past decade because of its inherent advantages of economic devices and low background noise. However, traditional assembly of photoelectric beacons, probes, and targets on the ITO electrode solid-liquid interface inevitably leads to time-consuming, limited selectivity, poor stability, and nonreproducibility. To overcome these drawbacks, in this work, a unique split-type PEC aptasensor for carcinoembryonic antigen (CEA) was developed in virtue of the sandwich-like structure comprised of magnetic-optical [email protected]@CdS-DNA1, CEA aptamer, and signal element SiO2-Au-DNA2. The sandwich-like structure is easily formed in the liquid phase and can be triggered by competition from low-abundance CEA, resulting in dissociation. By further photocurrent measurement in pure phosphate buffer saline, co-existing species can be effectively removed from the modified electrode, improving selectivity, stability, and repeatability. These advantages benefit from the preparation of uniform and monodispersed [email protected]@CdS and SiO2-Au particles, DNAs assembly, and an elegant design. Additionally, the as-designed signal-on PEC aptasensor is highly sensitive, short time-consuming, and economical, enabling the detection of CEA in serum specimens. It not only provides an alternative to CEA immunosensors, but also paves the way for high-performance PEC aptasensors.
Titanium dioxide (TiO2) nanomaterials have attracted much interest in life science and biological fields because of their excellent photocatalytic activity and good biocompatibility. However, owing to wide band-gap, photocatalysis of TiO2 can be only triggered by UV light. The limited transparent depth of UV light and the generated reactive oxygen species (ROS) cause inflammation response of skin tissue, thus posing two major challenges in the photocatalytic application of TiO2-based materials in drug delivery and other biotechnology fields. Here, we propose an upconversion-related strategy to enable the photocatalytic activity of TiO2 nanotubes in near-infrared (NIR) light and apply the system as controllable drug delivery platform. More importantly, the ROS-induced cytotoxicity and the preleaching of payload are significantly reduced on the as-proposed amphiphilic TiO2 nanotubes. The hydrophobic monolayers are served as a “cap” to provide protection for ROS-induced inflammation and long-term storability. This amphiphilic drug delivery system broadens the potential applications of TiO2-based nanomaterials in biomedicine.
Photothermal treatment (PTT) involving combination therapeutic modalities were recently emerged as an efficient alternative for combating biofilm. However, PTT-related local high temperature may destroy the surrounding healthy tissues. Herein, we present an all-in-one photo-therapeutic nanoplatform consisting of L-arginine (L-Arg), indocyanine green (ICG) and mesoporous polydopamine (MPDA), namely AI-MPDA, to eliminate the already-formed biofilm. The fabrication process included surface modification of MPDA with L-Arg and further adsorption of ICG via π-π stacking. Under near infrared (NIR) exposure, AI-MPDA not only generated heat, but also produced reactive oxygen species (ROS), causing cascade catalysis of L-Arg to release nitric oxide (NO). Under near infrared (NIR) irradiation, biofilm elimination was attributed to the NO-enhanced photodynamic therapy (PDT) and low-temperature PTT (≤ 45 °C). Notably, NIR-triggered all-in-one strategy resulted in severe destruction of bacterial membranes. The photo-therapeutic AI-MPDA also displayed good cytocompatibility. NIR-irradiated AI-MPDA nanoparticles not only prevented bacterial colonization, but also realized a rapid recovery of infected wound. More importantly, the all-in-one photo-therapeutic platform displayed effective biofilm elimination with an efficiency of around 100% in a abscess formation model. Overall, this low-temperature photo-therapeutic platform provides a reliable tool for combating already-formed biofilm in clinical applications.
In this research, a controlled release photoelectrochemical (PEC) immunosensor is proposed on the basis of novel encapsula-tion strategy by all inorganic semiconductor materials. The controlled-release transmit system has been prepared and repre-sented on account of group-functional mesoporous silica nanosphere (MSN), utilizing surface-functionalized cadmium sulfide (CdS) nanoparticles as mobilizable caps to encapsulate PEC electron donors (AA) within MSN mesoporous structure. This encapsulation strategy proceeds without enzyme, any acid / alkali to achieve the release of electron donor. The complex is formed by encapsulating AA in MSN with CdS ([email protected]) as signal-amplifier labeled on the secondary antibody. In addition, the immunological recognition process was performed in a 96-well plate, and the reciprocal interference between bio-recognition and PEC analysis could be eliminated through split-type framework. Bi2S3 sensitized porous In2O3 nanoparticles as substrate matrix provides a basic PEC response. The raised sensor shared a mensurable output of PCT concentration (as ex-ample) in the detection range of 0.001 ng/mL to 200 ng/mL along with limit of detection of 0.31 pg/mL. Featuring the novel method for electron released, this sensitive PEC strategy provides an innovative way potential application for other targets.
Biofilm has resulted in numerous obstinate clinical infections, posing severe threats to public health. It is urgent to develop original antibacterial strategies for eradicating biofilm. Herein, we develop a surface charge switchable supramolecular nanocarrier exhibiting pH-responsive penetration into acidic biofilm for nitric oxide (NO) synergistic photodynamic eradication of methicillin-resistant Staphylococcus aureus (MRSA) biofilm with negligible damage to healthy tissues under laser irradiation. Originally, by integrating the glutathione (GSH)-sensitive α-cyclodextrin (α-CD) conjugated nitric oxide (NO) prodrug (α-CD-NO) and chlorin e6 (Ce6) prodrug (α-CD-Ce6) into the pH-sensitive poly(ethylene glycol) (PEG) block polypeptide copolymer (PEG-(KLAKLAK)2-DA) via host-guest interaction, the supramolecular nanocarrier α-CD-Ce6-NO-DA is finely prepared. The supramolecular nanocarrier shows complete surface charge reversal from negative charge at physiological pH (7.4) to positive charge at acidic biofilm pH (5.5), promoting efficient penetration into biofilm. Once infiltrating into biofilm, the nanocarrier exhibits rapid NO release triggered by the overexpressed GSH in biofilm, which not only produces abundant NO for killing bacteria, but also reduces biofilm GSH level to improve photodynamic therapy (PDT) efficiency. On the other hand, NO can react with reactive oxygen species (ROS) to produce reactive nitrogen species (RNS), furtherly improving PDT efficiency. Due to the effective penetration into biofilm and depletion of biofilm GSH, the surface charge switchable GSH-sensitive NO nanocarrier can greatly improve the PDT efficiency at low photosensitizer dose and laser intensity and cause negligible side effect to healthy tissues. Considering the above advantages, the strategy developed in this work may offer great possibilities to fight against biofilm infections.
In this work, a series of Fe-based metal-organic frameworks (Fe-MOFs) were synthesized and served as Fenton-like catalysts for tetracycline hydrochloride (TC–HCl) degradation. Herein, for the first time, we have demonstrated that visible light can accelerate Fe(II)/Fe(III) cycle in the photo-Fenton system based on iron-oxo (Fe-O) clusters in frameworks. Among these Fe-MOFs, MIL-101 possessed the highest activity mainly ascribed to its largest specific surface area and pore volume, and the most coordinatively unsaturated iron sites. The synergistic effect in the MIL-101/H2O2/visible light system was derived from the efficient separation and migration of photogenerated carriers. Due to the function of solid acid catalysts, MIL-101 extended effective pH range up to 10.2 and exhibited good reusability and stability. Hydroxyl radicals generated from H2O2 coordinated at iron active sites were determined as the main reactive oxidative species and acceleration of Fe(II)/Fe(III) cycle was responsible for highly effective degradation of TC–HCl.
Tendon to bone (enthesis) rupture, which may cause disability and persistent pain, shows high rate of re‐rupture after surgical repair. Tendon or enthesis scaffolds have been widely studied, but few of these materials can recapitulate the tissue continuity. Thus, this study is conducted to prepare a triphasic decellularized bone‐fibrocartilage‐tendon (D‐BFT) composite scaffold. The D‐BFT scaffold is developed using a combination of physical, chemical, and enzymatic treatments using liquid nitrogen, Triton‐X 100, sodium‐dodecyl sulfate, and DNase I, which effectively removes the cell components while preserving the biological composite and microstructure. Moreover, the mechanical properties of D‐BFT are highly preserved and similar to those of the human Achilles tendon. Additionally, in vitro, mesenchymal stem cells (MSCs) adhered, proliferated, and infiltrated into the D‐BFT scaffold, and MSC differentiation is confirmed by up‐regulation of osteogenic‐related and tenogenic‐related genes. The repair outcomes are explored by applying the D‐BFT scaffold in the model of femur‐tibia defects in vivo, which shows good repair results. Thus, the D‐BFT scaffold developed in this study is a promising graft for enthesis regeneration. This study applies specific decellularization schemes for bone‐fibrocartilage‐tendon (BFT) triphasic composites based on corresponding tissue specificity, and the integrated structures and biocomponents of BFT scaffold after decellularization process with good biocompatibility and the ability to induce MSCs specific differentiations (osteogenic and myotendinous) in vitro and superiority ability to promote enthesis regeneration in vivo are well preserved.
Herein, a novel photoelectrochemical (PEC) assay was developed for sensitive detection of c-reactive protein (CRP) based on zirconium-based metal-organic framework (PCN-777) as the photoelectric material and thioflavine-T (Th-T) as the effective signal sensitizer coupled with rolling circle amplification (RCA). The inherent limitation of PCN-777 originated from its wide band gap could be effectively overcome by combining narrow band gap Th-T with PCN-777, thus presenting a significantly improved photo-current conversion efficiency compared to that of solitary PCN-777. Briefly, the synthesized PCN-777 with a homogeneous octahedron was firstly coated on the electrode surface, thereby providing an initial PEC response. Subsequently, target (CRP) was converted into primer strand via a simple protein converting procedure, and thus the obtained primer strand could trigger RCA on the sensing interface for generating abundant G-rich sequence, which would specifically bind with Th-T to form numerous steady G-quadruplex structure. The introduction of Th-T could result in a significantly enhanced PEC response for the quantitative detection of CRP. The designed PEC sensing for CRP assay exhibited a linear range of 50 fM to 50 nM with a detection limit of 16 fM. More importantly, the designed strategy offered a novel PEC analytical approach for sensitive detection of biomarkers in disease diagnosis, treatment monitoring and prognosis assessment.
This work demonstrates that the photoelectric response of defect-engineered TiO2-x modified with Au nanoparticles can be modulated by oxygen vacancy concentration and excitation wavelength. Anchoring strongly plasmonic Au nanoparticles to defect-engineered TiO2-x by DNA hybridization, several times plasmonic enhancement of photocurrent occurs under 585 nm excitation, and it is employed as a novel signaling mode for developing an improved photoelectrochemical sensing platform. This signaling mode combining with exonuclease III-assisted target recycling amplification exhibits excellent analytical per-formance, which provides a novel photoelectrochemical detection protocol.
Titanium dioxide (TiO2; as a potential photosensitizer) has good photocurrent performance and chemical stability, but often exhibits low utilization efficiency under ultraviolet (UV) region excitation. Herein, we devised a near-infrared (NIR) light-to-UV light-mediated photoelectrochemical (PEC) aptasensing platform for the sensitive detection of carcinoembryonic antigen (CEA) based on core-shell NaYF4:Yb,Tm@TiO2 upconversion microrods by coupling with target-triggered rolling circle amplification (RCA). The upconversion microrods synthesized through the hydrothermal reaction could act as a photosensing platform to convert the NIR excitation into UV emission for generation of photo-induced electrons. Target analyte was determined on functional magnetic bead by using the corresponding aptamers with a sandwich-type assay format. Upon target CEA introduction, a complex was first formed between capture aptamer-1-conjugated magnetic bead (Apt1-MB) and aptamer-2-primer DNA (Apt2-pDNA). Thereafter, the carried primer DNA by the aptamer-2 paired with linear padlock DNA to trigger the RCA reaction. The guanine (G)-rich product by RCA reaction was cleaved by exonuclease I and exonuclease III (Exos I/III), thereby resulting in the formation of numerous individual guanine bases to enhance the photocurrent of core-shell NaYF4:Yb,Tm@TiO2 upconversion microrods under NIR illumination (980 nm). Under optimal conditions, NIR light-mediated PEC aptasensing system could exhibit good photoelectrochemical response toward target CEA, and allowed for the detection of target CEA as low as 3.6 pg mL-1. High reproducibility and good accuracy were achieved for analysis of human serum specimens. Importantly, the NIR-activated PEC aptasensing scheme provides a promising platform for ultrasensitive detection of other biomolecules.
The detection methods and generation mechanisms of the intrinsic reactive oxygen species (ROS), i.e., superoxide anion radical (•O2–), hydrogen peroxide (H2O2), singlet oxygen (¹O2), and hydroxyl radical (•OH) in photocatalysis, were surveyed comprehensively. Consequently, the major photocatalyst used in heterogeneous photocatalytic systems was found to be TiO2. However, besides TiO2 some representative photocatalysts were also involved in the discussion. Among the various issues we focused on the detection methods and generation reactions of ROS in the aqueous suspensions of photocatalysts. On the careful account of the experimental results presented so far, we proposed the following apprehension: adsorbed •OH could be regarded as trapped holes, which are involved in a rapid adsorption–desorption equilibrium at the TiO2–solution interface. Because the equilibrium shifts to the adsorption side, trapped holes must be actually the dominant oxidation species whereas •OH in solution would exert the reactivity mainly for nonadsorbed reactants. The most probable routes of generating intrinsic ROS at the surfaces of two polymorphs of TiO2, anatase and rutile, were discussed along with some plausible rational reaction processes. In addition to the four major ROS, three ROS, that is organic peroxides, ozone, and nitric oxide, which are less common in photocatalysis are also briefly reviewed.
Metal–organic frameworks (MOFs) or porous coordination polymers (PCPs) are open, crystalline supramolecular coordination architectures with porous facets. These chemically tailorable framework materials
are the subject of intense and expansive research, and are particularly relevant in the fields of sensory materials and device engineering. As the subfield of MOF-based sensing has developed, many diverse chemical functionalities have been carefully and rationally implanted into the coordination nanospace of MOF materials. MOFs with widely varied fluorometric sensing properties have been developed using the design principles of crystal engineering and structure–property correlations, resulting in a large and rapidly growing body of literature. This work has led to advancements in a number of crucial sensing domains, including biomolecules, environmental toxins, explosives, ionic species, and many others. Furthermore, new classes of MOF sensory materials utilizing advanced signal transduction by devices based on MOF photonic crystals and thin films have been developed. This comprehensive review summarizes the topical developments in the field of luminescent MOF and MOF-based photonic crystals/thin film sensory materials.
Antibiotic resistance is a significant emerging health threat. Exacerbating this problem is the overprescription of antibiotics as well as a lack of development of new antibacterial agents. A paradigm shift toward the development of nonantibiotic agents that target the virulence factors of bacterial pathogens is one way to begin to address the issue of resistance. Of particular interest are compounds targeting bacterial AB toxins that have the potential to protect against toxin-induced pathology without harming healthy commensal microbial flora. Development of successful antitoxin agents would likely decrease the use of antibiotics, thereby reducing selective pressure that leads to antibiotic resistance mutations. In addition, antitoxin agents are not only promising for therapeutic applications, but also can be used as tools for the continued study of bacterial pathogenesis. In this review, we discuss the growing number of examples of chemical entities designed to target exotoxin virulence factors from important human bacterial pathogens.
Pore-forming toxins (PFTs) are virulence factors produced by many pathogenic bacteria and have long fascinated structural biologists, microbiologists and immunologists. Interestingly, pore-forming proteins with remarkably similar structures to PFTs are found in vertebrates and constitute part of their immune system. Recently, structural studies of several PFTs have provided important mechanistic insights into the metamorphosis of PFTs from soluble inactive monomers to cytolytic transmembrane assemblies. In this Review, we discuss the diverse pore architectures and membrane insertion mechanisms that have been revealed by these studies, and we consider how these features contribute to binding specificity for different membrane targets. Finally, we explore the potential of these structural insights to enable the development of novel therapeutic strategies that would prevent both the establishment of bacterial resistance and an excessive immune response.
The utilization of solar energy for the conversion of CO2 into valuable organic products is one of the best solutions to solve the problems of global warming and energy shortage. The development of photocatalysts capable of reducing CO2 under visible light, especially those containing earth-abundant metals, is signi ficant. Herein we report that a series of earth-abundant Fe-containing MOFs (MIL-101(Fe), MIL-53(Fe), MIL-88B(Fe)) show photocatalytic activity for CO2 reduction to give formate under visible light irradiation. The direct excitation of the Fe-O clusters in these MOFs induces the electron transfer from O2- to Fe3+ to form Fe2+, which is responsible for the photocatalytic CO2 reduction. Among the three investigated Fe-based MOFs, MIL-101(Fe) showed the best activity due to the existence of the coordination unsaturated Fe sites in its structure. All three amine-functionalized Fe-containing MOFs (NH2-MIL-101(Fe), NH2-MIL-53(Fe) and NH2-MIL-88B(Fe)) showed enhanced photocatalytic activity in comparison to the unfunctionalized MOF, due to the existence of dual excitation pathways: i.e., excitation of an NH2 functionality followed by an electron transfer to the Fe center in addition to the direct excitation of Fe-O clusters. (Chemical Equation Presented).
Antimicrobial peptides (AMPs) with non-specific membrane disrupting activities are thought to exert their antimicrobial activity as a result of their cationicity, hydrophobicity and α-helical or β-sheet structures. Chensinin-1, a native peptide from skin secretions of Rana chensinensis, fails to manifest its desired biological properties because its low hydrophobic nature and an adopted random coil structure in a membrane-mimetic environment. In this study, chensinin-1b was designed by rearranging the amino acid sequence of its hydrophilic/polar residues on one face and its hydrophobic/nonpolar residues on the opposite face according to its helical diagram, and by replacing three Gly residues with three Trp residues. Introduction of Trp residues significantly promoted the binding of the peptide to the bacterial outer membrane and exerted bactericidal activity through cytoplasmic membrane damage. Chensinin-1b demonstrates higher antimicrobial activity and greater cell selectivity than its parent peptide, chensinin-1. The electrostatic interactions between chensinin-1b and lipopolysaccharide (LPS) may have facilitated the uptake of the peptide into Gram-negative cells and be also helpful to disrupt the bacterial cytoplasmic membrane, as evidenced by depolarisation of the membrane potential and leakage of calceins from the liposomes of Escherichia coli and Staphylococcus aureus. Chensinin-1b was also found to penetrate mouse skin and was also effective in vivo, as measured by hydroxyproline levels in a wound infection mouse model, and could therefore act as an anti-infective agent for wound healing.
Copyright © 2014 Elsevier Ltd. All rights reserved.
The quantum yield of hydroxyl radical (⋅OH) production during TiO2 photocatalysis was estimated to be 7×10−5 in aqueous solution by means of a method using terephthalic acid as a fluorescence probe. This value is much lower than the quantum yield of ordinary photocatalytic reactions (∼10−2). Conversely, the quantum yield of hole generation estimated by iodide ion oxidation was equivalent (5.7×10−2) to that of ordinary photocatalytic reactions. This implies that oxidative reactions on TiO2 photocatalyst occur mainly via photogenerated holes, not via ⋅OH.
We report a new approach to selectively deliver antimicrobials to the sites of bacterial infections by utilizing bacterial toxins to activate drug release from gold nanoparticle-stabilized phospholipid liposomes. The binding of chitosan-modified gold nanoparticles to the surface of liposomes can effectively prevent them from fusing with one another and from undesirable payload release in regular storage or physiological environments. However, once these protected liposomes "see" bacteria that secrete toxins, the toxins will insert into the liposome membranes and form pores, through which the encapsulated therapeutic agents are released. The released drugs subsequently impose antimicrobial effects on the toxin-secreting bacteria. Using methicillin-resistant Staphylococcus aureus (MRSA) as a model bacterium and vancomycin as a model anti-MRSA antibiotic, we demonstrate that the synthesized gold nanoparticle-stabilized liposomes can completely release the encapsulated vancomycin within 24 h in the presence of MRSA bacteria and lead to inhibition of MRSA growth as effective as an equal amount of vancomycin-loaded liposomes (without nanoparticle stabilizers) and free vancomycin. This bacterial toxin enabled drug release from nanoparticle-stabilized liposomes provides a new, safe, and effective approach for the treatment of bacterial infections. This technique can be broadly applied to treat a variety of infections caused by bacteria that secrete pore-forming toxins.
The utility of nitric oxide (NO)-releasing silica nanoparticles as novel antibacterial agents is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently labeled NO-releasing nanoparticles associated with the bacterial cells, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the advantage of delivering NO via nanoparticles for antimicrobial applications.
This work was supported by the National Natural Science Foundation of China (NSFC, Grant No. 20673112), the National Basic Research Program of China (Grant Nos. 2003CB615806 and 2003CB214504), and the Knowledge Innovation Program of the Chinese Academy of Sciences (Grant No. DICP K2006E2). We thank Fengtao Fan for help with the illustrations and Zili Wu for discussions.