ABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) is the primary pathogenic agent responsible for epidermal wound infection and suppuration, seriously threatening the life and health of human beings. To address this fundamental challenge, we propose a heterojunction nanocomposite (Ca-CN/MnS) comprised of Ca-doped g-C3N4 and MnS for the therapy of MRSA-accompanied wounds. The Ca doping leads to a reduction in both the bandgap and the singlet state S1-triplet state T2 energy gap (ΔEST). The Ca doping also facilitates the two-photon excitation, thus remarkably promoting the separation and transfer of 808 nm near-infrared (NIR) light-triggered electron-hole pairs together with the built-in electric field. Thereby, the production of reactive oxygen species and heat are substantially augmented nearby the nanocomposite under 808 nm NIR light irradiation. Consequently, an impressive photocatalytic MRSA bactericidal efficiency of 99.98 ± 0.02â¯% is achieved following exposure to NIR light for 20 min. The introduction of biologically functional elements (Ca and Mn) can up-regulate proteins such as pyruvate kinase (PKM), L-lactate dehydrogenase (LDHA), and calcium/calmodulin-dependent protein kinase (CAMKII), trigger the glycolysis and calcium signaling pathway, promote cell proliferation, cellular metabolism, and angiogenesis, thereby expediting the wound-healing process. This heterojunction nanocomposite, with its precise charge-transfer pathway, represents a highly effective bactericidal and bioactive system for treating multidrug-resistant bacterial infections and accelerating tissue repair. STATEMENT OF SIGNIFICANCE: Due to the bacterial resistance, developing an antibiotic-free and highly effective bactericidal strategy to treat bacteria-infected wounds is critical. We have designed a heterojunction consisting of calcium doped g-C3N4 and MnS (Ca-CN/MnS) that can rapidly kill methicillin-resistant Staphylococcus aureus (MRSA) without damaging normal tissue through a synergistic effect of two-photon stimulated photothermal and photodynamic therapy. In addition, the release of trace amounts of biofunctional elements Mn and Ca triggers glycolysis and calcium signaling pathways that promote cellular metabolism and cell proliferation, contributing to tissue repair and wound healing.
Subject(s)
Calcium , Glycolysis , Methicillin-Resistant Staphylococcus aureus , Methicillin-Resistant Staphylococcus aureus/drug effects , Glycolysis/drug effects , Animals , Calcium/metabolism , Staphylococcal Infections/drug therapy , Phototherapy , Wound Infection/microbiology , Wound Infection/pathology , Wound Infection/drug therapy , Humans , Nanocomposites/chemistry , Wound Healing/drug effects , Mice , Infrared RaysABSTRACT
Multi-drug resistant bacterial infections pose a significant threat to human health. Thus, the development of effective bactericidal strategies is a pressing concern. In this study, a ternary heterostructure (Zn-CN/P-GO/BiS) comprised of Zn-doped graphite phase carbon nitride (g-C3N4), phosphorous-doped graphene oxide (GO) and bismuth sulphide (Bi2S3) is constructed for efficiently treating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound. Zn doping-induced defect sites in g-C3N4 results in a reduced band gap (ΔE) and a smaller energy gap (ΔEST) between the singlet state S1 and triplet state T1, which favours two-photon excitation and accelerates electron transfer. Furthermore, the formation of an internal electric field at the ternary heterogeneous interface optimizes the charge transfer pathway, inhibits the recombination of electron-hole pairs, improves the photodynamic effect of g-C3N4, and enhances its catalytic performance. Therefore, the Zn-CN/P-GO/BiS significantly augments the production of reactive oxygen species and heat under 808 nm NIR (0.67 W cm-2) irradiation, leading to the elimination of 99.60% ± 0.07% MRSA within 20 min. Additionally, the release of essential trace elements (Zn and P) promotes wound healing by activating hypoxia-inducible factor-1 (HIF-1) and peroxisome proliferator-activated receptors (PPAR) signaling pathways. This work provides unique insight into the rapid antibacterial applications of trace element doping and two-photon excitation.
ABSTRACT
Osteomyelitis caused by deep tissue infections is difficult to cure through phototherapy due to the poor penetration depth of the light. Herein, Cu/C/Fe3O4-COOH nanorod composites (Cu/C/Fe3O4-COOH) with nanoscale tip convex structures are successfully fabricated as a microwave-responsive smart bacteria-capture-killing vector. Cu/C/Fe3O4-COOH exhibited excellent magnetic targeting and bacteria-capturing ability due to its magnetism and high selectivity affinity to the amino groups on the surface of Staphylococcus aureus (S. aureus). Under microwave irradiation, Cu/C/Fe3O4-COOH efficiently treated S. aureus-infected osteomyelitis through the synergistic effects of microwave thermal therapy, microwave dynamic therapy, and copper ion therapy. It is calculated the electric field intensity in various regions of Cu/C/Fe3O4-COOH under microwave irradiation, demonstrating that it obtained the highest electric field intensity on the surface of copper nanoparticles of Cu/C/Fe3O4-COOH due to its high-curvature tips and metallic properties. This led to copper nanoparticles attracted more charged particles compared with other areas in Cu/C/Fe3O4-COOH. These charges are easier to escape from the high curvature surface of Cu/C/Fe3O4-COOH, and captured by adsorbed oxygen, resulting in the generation of reactive oxygen species. The Cu/C/Fe3O4-COOH designed in this study is expected to provide insight into the treatment of deep tissue infections under the irradiation of microwave.
Subject(s)
Nanoparticles , Osteomyelitis , Staphylococcal Infections , Humans , Staphylococcus aureus , Copper/chemistry , Microwaves/therapeutic use , Nanoparticles/chemistry , Staphylococcal Infections/therapy , Osteomyelitis/therapyABSTRACT
Bacterial infection is an urgent public health problem. We design a novel photo-responsive hybrid material by growing small molecules of curcumin (Cur) in situ on a sea urchin-like Bi2S3 surface by a one-step hydrothermal reaction method, thus forming an organic-inorganic hybrid material with interfacial contact. The Bi2S3/Cur hybrid material has good antibacterial effect under 808 nm near-infrared (NIR) light irradiation. The antibacterial mechanism is that the electron redistribution at the interface of Bi2S3/Cur excited by 808 nm NIR light will cause a large number of electrons to gather on the side of Bi2S3, forming an internal electric field to drive the excited electrons from Bi2S3 to Cur, which accelerates the separation of photoexcited electron-hole pairs and enhances the production of reactive oxygen species (ROS). In conclusion, due to these synergistic effects of the photothermal properties of Bi2S3, the production of more ROS and the release of small molecules of Cur from traditional Chinese medicine in Bi2S3/Cur, the antibacterial efficacy against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) is 99.96% and 99.03%, respectively. In vivo experiments in animals show that Bi2S3/Cur can reduce the inflammatory response and promote wound healing. This paper presents a simple, rapid and safe strategy for the treatment of wound infections with near-infrared light.
Subject(s)
Curcumin , Animals , Curcumin/pharmacology , Staphylococcus aureus , Escherichia coli , Reactive Oxygen Species , Wound Healing , Anti-Bacterial Agents/pharmacology , Sea UrchinsABSTRACT
Owing to its flexibility and high treatment efficiency, phototherapy is rapidly emerging for treating bacteria-induced diseases, but how to improve the sensitivity of bacteria to reactive oxygen species (ROS) and heat simultaneously to kill bacteria under mild conditions is still a challenge. Herein, we designed a NIR light catalyst (Bi2S3-S-nitrosothiol-acetylcholine (BSNA)) by transforming â¢O2- into peroxynitrite in situ, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite in situ possessed a stronger ability to penetrate cell membranes and antioxidant capacity. The BSNA nanoparticles (NPs) inhibited the bacterial glucose metabolic process through down-regulated xerC/xerD expression and disrupted the HSP70/HSP90 secondary structure through nitrifying TYR179. Additionally, the synergistic effect of the designed BSNA and clinical antibiotics increased the antibacterial activity. In the case of tetracycline-class antibiotics, BSNA NPs induced phenolic hydroxyl group structure changes and inhibited the interaction between tetracycline and targeted t-RNA recombinant protein. Besides, BSNA stimulated production of more CD8+ T cells and reduced common complications in peritonitis, which provided immunotherapy activity. The targeted and anti-infective effect of BSNA suggested that we propose a nanotherapeutic strategy to achieve more efficient synergistic therapy under mild temperatures.
Subject(s)
Bacterial Infections , Nanoparticles , S-Nitrosothiols , Acetylcholine , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Antioxidants , Bacteria/metabolism , Bacterial Infections/drug therapy , Bismuth , CD8-Positive T-Lymphocytes , Glucose , Humans , Immunotherapy , Nanoparticles/chemistry , Peroxynitrous Acid , Phototherapy , RNA , Reactive Oxygen Species/metabolism , Recombinant Proteins , Sulfides/chemistry , Sulfides/pharmacology , Sulfides/therapeutic use , TetracyclinesABSTRACT
Owing to the existence of the outer membrane barrier, most antibacterial agents cannot penetrate Gram-negative bacteria and are ineffective. Here, we report a general method for narrow-spectrum antibacterial Garcinia nanoparticles that can only be effective to kill Gram-positive bacteria, to effectively eliminate Gram-negative bacteria by creating transient nanopores in bacterial outer membrane to induce drug entry under microwaves assistance. In vitro, under 15 min of microwaves irradiation, the antibacterial efficiency of Garcinia nanoparticles against Escherichia coli can be enhanced from 6.73% to 99.48%. In vivo, MV-assisted GNs can effectively cure mice with bacterial pneumonia. The combination of molecular dynamics simulation and experimental results reveal that the robust anti-E. coli effectiveness of Garcinia nanoparticles is attributed to the synergy of Garcinia nanoparticles and microwaves. This work presents a strategy for effectively treating both Gram-negative and Gram-positive bacteria co-infected pneumonia using herbal medicine nanoparticles with MV assistance as an exogenous antibacterial auxiliary.
Subject(s)
Garcinia , Nanoparticles , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Escherichia coli , Gram-Negative Bacteria , Gram-Positive Bacteria , Mice , Microbial Sensitivity Tests , MicrowavesABSTRACT
Bacterial infections have seriously threatened human health and the abuse of natural or artificial antibiotics leads to bacterial resistance, so development of a new generation of antibacterial agents and treatment methods is urgent. 2D molybdenum sulfide (MoS2 ) has good biocompatibility, high specific surface area to facilitate surface modification and drug loading, adjustable energy bandgap, and high near-infrared photothermal conversion efficiency (PCE), so it is often used for antibacterial application through its photothermal or photodynamic effects. This review comprehensively summarizes and discusses the fabrication processes, structural characteristics, antibacterial performance, and the corresponding mechanisms of MoS2 -based materials as well as their representative antibacterial applications. In addition, the outlooks on the remaining challenges that should be addressed in the field of MoS2 are also proposed.
Subject(s)
Escherichia coli , Molybdenum , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Disulfides/chemistry , Disulfides/pharmacology , Humans , Molybdenum/chemistry , Molybdenum/pharmacology , PhototherapyABSTRACT
Large doses and long duration are often required for herbal medicines to kill bacteria effectively. Herein, a photoacoustic interfacial engineering strategy was utilized to endow curcumin (Cur, a kind of herbal medicine) with rapid and highly effective bacteria-killing efficacy, in which Cur was combined with CuS to form a hybrid material of CuS/Cur with tight contact through in situ nucleation and growth on the petaloid CuS surface. Due to the different work functions of CuS and Cur, the interfacial electrons were redistributed, i.e., a large number of electrons gathered on the side of CuS. In contrast, the holes gathered on the side of Cur after contact. An internal electric field was formed to drive the excited electrons to transfer from CuS to Cur, thus enhancing the separation of electron-hole pairs. Besides exerting the drug nature of Cur itself, the CuS/Cur hybrid also had photo-sono responsive ability, which endowed the hybrid with photothermal, photodynamic, and sonodynamic effects. Therefore, this Cur-based hybrid killed 99.56% of Staphylococcus aureus and 99.48% of Escherichia coli under 808 nm near-infrared light irradiation and ultrasound successively for 15 min, which was ascribed to the synergy of ROS, hyperthermia, and released Cu2+ together with the drug properties of Cur. This work provides a strategy to enhance the therapeutic effects of herbal medicines against pathogenic bacterial infections by exciting the intrinsic properties of herbal medicines as materials through a photo-sono interfacial engineering strategy.
Subject(s)
Nanomedicine , Nanoparticles , Copper/pharmacology , Phototherapy , Staphylococcus aureus , Escherichia coli , Nanoparticles/therapeutic useABSTRACT
Core-shell nanoparticles (CSNs) have numerous intriguing properties for advanced device applications, while it remains challenging to directly grow them from a solid substrate. Here, we report a simple mussel-bioinspired solid chemistry strategy for in-situ synthesis of CSNs that are substrate anchored and morphologically tunable for wide-ranging biotechnological applications. Briefly, silver titanate was hydrothermally grown on template titanium and subjected to reaction with mussel-derived dopamine. The synergistic reactivity between silver titanate and dopamine prompted nanosilver/polydopamine (nAg/PD) CSNs to spontaneously assemble and grow on substrate. These CSNs possessed reaction time-dependent dimensions and morphologies, which were related to differing physiochemical properties and biological behaviors. Specifically, the CSNs-modified substrates demonstrated enhanced protein affinity and durable radical scavenging properties. In addition, they manifested remarkable yet robust release-killing and anti-biofilm activities against pathogenic Staphylococcus aureus bacteria. More delightedly, the surface-engineered substrates guaranteed the victory of the anti-infective battle of osteoblastic cells during cell/bacteria coculture, promising applications in implantable medical devices. The adaptability of this strategy was demonstrated by modifying complicated 3D-printed macroporous tissue engineering scaffolds. Intriguingly, the CSNs-modified scaffolds exhibited photothermal performances that bode well for phototherapy. To sum, our strategy combines the simplicity of synthesis modality, the controllability of core-shell silver structures, and the versatility of material functions. The resulting assemblies can enrich the library of nAg-based core-shell engineered nanomaterials.
Subject(s)
Bivalvia , Silver , Animals , Polymers , Staphylococcus aureus , TitaniumABSTRACT
Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over the world. The commonly used antibiotic therapy cannot effectively treat these diseases within a short time, and also bring about adverse effects such as drug resistance and immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to treat these diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) or induce a temperature increase, which leads to the death of targeted cells. These two kinds of killing strategies are referred to as photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. So far, many photo-responsive agents have been developed. Among them, the metal-organic framework (MOF) is becoming one of the most promising photo-responsive materials because its structure and chemical compositions can be easily modulated to achieve specific functions. MOFs can have intrinsic photodynamic or photothermal ability under the rational design of MOF construction, or serve as the carrier of therapeutic agents, owing to its tunable porosity. MOFs also provide feasibility for various combined therapies and targeting methods, which improves the efficiency of phototherapy. In this review, we firstly investigated the principles of phototherapy, and comprehensively summarized recent advances of MOF in PDT, PTT and synergistic therapy, from construction to modification. We expect that our demonstration will shed light on the future development of this field, and bring it one step closer to clinical trials.
Subject(s)
Antineoplastic Agents/pharmacology , Metal-Organic Frameworks/pharmacology , Neoplasms/drug therapy , Photosensitizing Agents/pharmacology , Animals , Antineoplastic Agents/chemistry , Cell Survival/drug effects , Humans , Metal-Organic Frameworks/chemistry , Neoplasms/metabolism , Neoplasms/pathology , Photochemotherapy , Photosensitizing Agents/chemistry , Reactive Oxygen Species/metabolismABSTRACT
Sonodynamic therapy (SDT) is considered to be a potential treatment for various diseases including cancers and bacterial infections due to its deep penetration ability and biosafety, but its SDT efficiency is limited by the hypoxia environment of deep tissues. This study proposes creating a potential solution, sonothermal therapy, by developing the ultrasonic interfacial engineering of metal-red phosphorus (RP), which has an obviously improved sonothermal ability of more than 20 °C elevation under 25 min of continuous ultrasound (US) excitation as compared to metal alone. The underlying mechanism is that the mechanical energy of the US activates the motion of the interfacial electrons. US-induced electron motion in the RP can efficiently transfer the US energy into phonons in the forms of heat and lattice vibrations, resulting in a stronger US absorption of metal-RP. Unlike the nonspecific heating of the cavitation effect induced by US, titanium-RP can be heated in situ when the US penetrates through 2.5 cm of pork tissue. In addition, through a sonothermal treatment in vivo, bone infection induced by multidrug-resistant Staphylococcus aureus (MRSA) is successfully eliminated in under 20 min of US without tissue damage. This work provides a new strategy for combating MRSA by strong sonothermal therapy through US interfacial engineering.
Subject(s)
Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Engineering , Methicillin-Resistant Staphylococcus aureus/drug effects , Phosphorus/chemistry , Ultrasonic Therapy , Reactive Oxygen Species/metabolismABSTRACT
Both phototherapy via photocatalysts and physical puncture by artificial nanostructures are promising substitutes for antibiotics when treating drug-resistant bacterial infectious diseases. However, the photodynamic therapeutic efficacy of photocatalysts is seriously restricted by the rapid recombination of photogenerated electron-hole pairs. Meanwhile, the nanostructures of physical puncture are limited to two-dimensional (2D) platforms, and they cannot be fully used yet. Thus, this research developed a synergistic system of Ag3PO4 nanoparticles (NPs), decorated with black urchin-like defective TiO2 (BU-TiO2-X/Ag3PO4). These NPs had a decreased bandgap compared to BU-TiO2-X, and BU-TiO2-X/Ag3PO4 (3:1) exhibited the lowest bandgap and the highest separation efficiency for photogenerated electron-hole pairs. After combination with BU-TiO2-X, the photostability of Ag3PO4 improved because the oxygen vacancy of BU-TiO2-X retards the reduction of Ag+ in Ag3PO4 into Ag0, thus reducing its toxicity. In addition, the nanospikes on the surface of BU-TiO2-X can, from all directions, physically puncture bacterial cells, thus assisting the hybrid's photodynamic therapeutic effects, alongside the small amount of Ag+ released from Ag3PO4. This achieves synergy, endowing the hybrid with high antibacterial efficacy of 99.76 ± 0.15% and 99.85 ± 0.09% against Escherichia coli and Staphylococcus aureus, respectively, after light irradiation for 20 min followed by darkness for 12 h. It is anticipated that these findings may bring new insight for developing synergistic treatment strategies against bacterial infectious diseases or pathogenic bacterial polluted environments.
ABSTRACT
A light-inspired hydroxyapatite (Hap)/nitrogen-doped carbon dots (NCDs) modified graphene oxide (GO) heterojunction film is developed, which shows a promoted separation of interfacial electrons and holes and an inhibited recombination efficiency via hole depletion. The metabolism of bacteria on this film is significantly inhibited under light irradiation, due to the enhanced photocatalytic and photothermal effects. In addition, the electron transfer from the plasmonic membrane to the GO/NCD/Hap film further inhibits the adenosine triphosphate process of bacteria, thus leading to the synergetic antibacterial efficacy. Meanwhile, the electron transfer between film and cell membrane induces the Ca2+ flow after irradiation, which can promote the migration and proliferation of cells and alkaline phosphatase enhancement, thus favoring the tissue reconstruction. An in vivo test discloses that the vascular injury repair is achieved through the Ca2+-activated PLCγ1/ERK pathway, identified by the enhanced CD31 expression. Moreover, the increased CD4+/CD8+ lymphocytes are ameliorative by activating the PI3K/P-AKT pathway. Consequently, the electron transfer boosts the synergic photodynamic and photothermal therapeutic effects for bacterial infection by Ca2+ flow for immunotherapy. This mild phototherapy approach with GO/NCDs/Hap, which can simultaneously repair injured vessels and relieve inflammation reactions, will increase the clinical application of noninvasive phototherapy in the near future.
ABSTRACT
Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe3O4/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe3O4/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.
Subject(s)
Magnetite Nanoparticles/therapeutic use , Microwaves/therapeutic use , Osteomyelitis/drug therapy , Staphylococcal Infections/drug therapy , Animals , Anti-Bacterial Agents/therapeutic use , Drug Delivery Systems/methods , Drug Therapy/methods , Ferrosoferric Oxide/therapeutic use , Gentamicins/therapeutic use , Methicillin-Resistant Staphylococcus aureus/drug effects , Nanotubes, Carbon , Osteomyelitis/microbiology , RabbitsABSTRACT
Polyetheretherketone has been widely used for bone defect repair, whereas failures may happen due to implant loosening and infection. Thus, PEEK implant with multi-function (osteogenesis, angiogenesis, and bacteria-killing) is essential to solve this problem. Herein, copper oxide microspheres (µCuO) decorated with silver nanoparticles (nAg) were constructed on porous PEEK surface via silk fibroin. In vitro studies highlighted the pH controlled release ability of this coating. It liberated a high dose of Cu2+ and Ag+ at low pH environment (pH 5.0), leading to 99.99% killing of planktonic bacteria and complete eradication of sessile bacteria, avoiding biofilm formation. Under physiological environment (pH 7.4), a lower amount of leaked metal ions induced promoted ALP production, collagen secretion, and calcium deposition, as well as NO production, which indicated potentiated osteogenesis and angiogenesis. In vivo results displayed the highest new bone volume around, and the appearance of new bone inside porous structure of, PEEK implant with this coating in rabbit tibia, signified the abilities of this coating to promote bone regeneration and osseointegration. Our study established solid support for implants with this coating to be a successful bone defect repair solution. STATEMENT OF SIGNIFICANCE: In this study, CuO/Ag micro/nano particles were incorporated into the porous surface of PEEK through polydopamine and silk fibroin layers. The design of this coating conferred pH-controlled release behavior to Cu2+ and Ag+. High dose of metal ions were released at pH 5.0, which presented synergistic antibacterial ability and killed 99.99% of planktonic bacteria. Low concentration of metal ions were controlled by this coating at physiological environment, which potentiated osteodifferentiation of Ad-MSC in vitro and led to complete integration of implant with bone tissue in vivo.
Subject(s)
Fibroins , Metal Nanoparticles , Animals , Anti-Bacterial Agents/pharmacology , Benzophenones , Copper , Fibroins/pharmacology , Hydrogen-Ion Concentration , Ketones/pharmacology , Osteogenesis , Polyethylene Glycols , Polymers , Rabbits , Silver/pharmacologyABSTRACT
Clinically, methicillin-resistant Staphylococcus aureus (MRSA) biofilm infection inevitably induces the failure of bone implants. Herein, a hydrophilic and viscous hydrogel of poly(vinyl alcohol) modified with chitosan, polydopamine, and NO release donor was formed on a red phosphorus nanofilm deposited on a titanium implant (Ti-RP/PCP/RSNO). Under the irradiation of near-infrared light (NIR), peroxynitrite (â¢ONOO-) was formed by the reaction between the released NO and superoxide (â¢O2-) produced by the RP nanofilm. Specifically, we revealed the antibacterial mechanism of the ONOO- against the MRSA biofilm. In addition, osteogenic differentiation was promoted and inflammatory polarization was regulated by the released NO without NIR irradiation through upregulating the expression of Opn and Ocn genes and TNF-α. The MRSA biofilm was synergistically eradicated by â¢ONOO-, hyperthermia, and â¢O2- under NIR irradiation as well as the immunoreaction of the M1 polarization. The in vivo results also confirmed the excellent osteogenesis and biofilm eradication by released NO from the RP/PCP/RSNO system under NIR irradiation, indicating the noninvasive tissue reconstruction of MRSA-infected tissues through phototherapy and immunotherapy.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Biofilms , Immunotherapy , Osteogenesis , PhototherapyABSTRACT
Titanium-based endosseous implants with high antibacterial and osseointegration activities are extremely required in clinics. To achieve this line, herein the doped coatings with three kinds of Zn doses were micro-arc oxidized (MAOed) on Ti. They were examined to reveal a bilayered structure, in which the outer layer consisted completely of the amorphism comprising elements of Ti, O and Zn with Zn doped in the form of weaken Zn-O bonds, and the underlying layer was partially crystallized with nanocrystalline TiO2 and Zn2TiO4 to embed an amorphous matrix. While the Zn doped doses of the surface amorphous layers increased with elevating the MAOed voltages, the weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of reactive oxide species (ROS) on the coatings. The enhanced HO⢠and O2-⢠formation on the elevated voltage MAOed coatings caused serious break of the cell walls and plasma membranes of S. aureus. In parallel, the enhanced Zn2+ release and extracellular H2O2 formation led to the enhanced intracellular ROS level of S. aureus, further aggravating the damage of plasma membrane, resulting in bacteria death. On contrary to the overdose of Zn doped coating, the moderate doses of Zn doped coatings did not induce additional intracellular ROS and attenuate viability and proliferation of osteoblasts in vitro, and promoted osseointegration in both S. aureus-uninfected and infected rat tibias, which ascribed to the strong antibacterial activity and un-attenuated cell function of the coatings in the infected case. STATEMENT OF SIGNIFICANCE: (1) The Zn-doped coatings revealed a bilayered structure of the surface layer comprising the Ti, O and Zn constructed amorphism with Zn in the form of weaken Zn-O bonds, and the underlying layer comprising nanocrystalline TiO2 and Zn2TiO4 to embed amorphous matrix. (2) The weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of ROS on the coatings. (3) The enhanced Zn2+ release and ROS formation on the coatings killed S. aureus by inducing serious break of their cell walls and plasma membranes. This effect in combination of un-attenuated osteoblast proliferation endowed the moderate Zn doped coatings with enhanced osseointegration in S. aureus-infected rat tibias.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Coated Materials, Biocompatible/therapeutic use , Osseointegration/drug effects , Tibia/microbiology , Titanium/therapeutic use , Zinc/therapeutic use , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/toxicity , Escherichia coli/drug effects , Mice , Microbial Sensitivity Tests , Osteoblasts/drug effects , RAW 264.7 Cells , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Staphylococcus aureus/drug effects , Titanium/chemistry , Titanium/toxicity , Zinc/chemistry , Zinc/toxicityABSTRACT
Bacterial infection is seriously threatening human health all over the world, especially with the emergence of increasing drug-fast bacteria. It is urgent to develop a drug-free strategy to kill bacteria rapidly and efficiently. In this work, humic acid (HuA) encapsulated zeolitic imidazole framework-8 (ZIF-8) (HuA@ZIF-8) nanocomposites are synthesized by the in-situ growth of ZIF-8 on the surface of polyvinylpyrrolidone (PVP)-modified HuA. The synthesized nanocomposites possesses good photothermal effects, i.e., the temperature increased to 59.4⯰C under the particle concentration of 1000⯵g/mL with 10â¯min NIR irradiation. In addition, NIR irradiation can also control the release of Zn2+ from the composites. The good photothermal effects originate from HuA that can effectively absorb NIR light. The controlled release of Zn2+ is ascribed to the induced-dissociation of ZIF-8 under NIR light irradiation. The synergistic action of photothermal therapy and release of zinc ions contributes to the excellent antibacterial efficiency of HuA@ZIF-8 within a short time, i.e. 99.59 % and 99.37 % against Staphylococcus aureus and Escherichia coli with 20â¯min NIR irradiation, respectively. This work provides a promising strategy to develop a light-responsive platform with good biodegradability and low cost for rapid and effective sterilization.
Subject(s)
Anti-Bacterial Agents/pharmacology , Humic Substances/microbiology , Metal-Organic Frameworks/pharmacology , Phototherapy , Zinc/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Imidazoles/chemistry , Imidazoles/pharmacology , Metal-Organic Frameworks/chemistry , Microbial Sensitivity Tests , Particle Size , Staphylococcus aureus/drug effects , Surface Properties , Zeolites/chemistry , Zeolites/pharmacology , Zinc/chemistryABSTRACT
Biofilms have been related to the persistence of infections on medical implants, and these cannot be eradicated because of the resistance of biofilm structures. Therefore, a biocompatible phototherapeutic system is developed composed of MoS2, IR780 photosensitizer, and arginine-glycine-aspartic acid-cysteine (RGDC) to safely eradicate biofilms on titanium implants within 20 min. The magnetron-sputtered MoS2 film possesses excellent photothermal properties, and IR780 can produce reactive oxygen species (ROS) with the irradiation of near-infrared (NIR, λ = 700-1100 nm) light. Consequently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT), assisted by glutathione oxidation accelerated by NIR light, can provide synergistic and rapid killing of bacteria, i.e., 98.99 ± 0.42% eradication ratio against a Staphylococcus aureus biofilm in vivo within 20 min, which is much greater than that of PTT or PDT alone. With the assistance of ROS, the permeability of damaged bacterial membranes increases, and the damaged bacterial membranes become more sensitive to heat, thus accelerating the leakage of proteins from the bacteria. In addition, RGDC can provide excellent biosafety and osteoconductivity, which is confirmed by in vivo animal experiments.
ABSTRACT
Patients often face the challenge of antibiotic-resistant bacterial infections and lengthy tissue reconstruction after surgery. Herein, human hair-melanosome derivatives (HHMs), comprising keratins and melanins, are developed using a simple "low-temperature alkali heat" method for potentially personalized therapy. The mulberry-shaped HHMs have an average width of â¼270 nm and an average length of â¼700 nm, and the negatively charged HHMs can absorb positively charged Lysozyme (Lyso) to form the HHMs-Lyso composites through electrostatic interaction. These naturally derived biodegradable nanostructures act as exogenous killers to eliminate methicillin-resistant Staphylococcus aureus (MRSA) infection with a high antibacterial efficacy (97.19 ± 2.39%) by synergistic action of photothermy and "Lyso-assisted anti-infection" in vivo. Additionally, HHMs also serve as endogenous regulators of collagen alpha chain proteins through the "protein digestion and absorption" signaling pathway to promote tissue reconstruction, which was confirmed by quantitative proteomic analysis in vivo. Notably, the 13 upregulated collagen alpha chain proteins in the extracellular matrix (ECM) after HHMs treatment demonstrated that keratin from HHMs in collagen-dependent regulatory processes serves as a notable contributor to augmented wound closure. The current paradigm of natural material-tissue interaction regulates the cell-ECM interaction by targeting cell signaling pathways to accelerate tissue repair. This work may provide insight into the protein-level pathways and the potential mechanisms involved in tissue repair.