Bacteria-Activated Theranostic Nanoprobes against Methicillin-Resistant Staphylococcus aureus Infection
TL;DR: It is demonstrated that MRSA can effectively pull out the vancomycin-modified polyelectrolyte-cypate complexes from silica nanoparticles and draw them onto their own surface, changing the state of cypate from off to on and leading to in vitro MRSA-activated near-infrared fluorescence (NIRF) and photothermal elimination involving bacterial cell wall and membrane disruption.
Abstract: Despite numerous advanced imaging and sterilization techniques available nowadays, the sensitive in vivo diagnosis and complete elimination of drug-resistant bacterial infections remain big challenges. Here we report a strategy to design activatable theranostic nanoprobes against methicillin-resistant Staphylococcus aureus (MRSA) infections. This probe is based on silica nanoparticles coated with vancomycin-modified polyelectrolyte-cypate complexes (SiO2-Cy-Van), which is activated by an interesting phenomenon of bacteria-responsive dissociation of the polyelectrolyte from silica nanoparticles. Due to the aggregation of hydrophobic cypate fluorophores on silica nanoparticles to induce ground-state quenching, the SiO2-Cy-Van nanoprobes are nonfluorescent in aqueous environments. We demonstrate that MRSA can effectively pull out the vancomycin-modified polyelectrolyte-cypate complexes from silica nanoparticles and draw them onto their own surface, changing the state of cypate from off (aggregation) to on (disaggregation) and leading to in vitro MRSA-activated near-infrared fluorescence (NIRF) and photothermal elimination involving bacterial cell wall and membrane disruption. In vivo experiments show that this de novo-designed nanoprobe can selectively enable rapid (4 h postinjection) NIRF imaging with high sensitivity (105 colony-forming units) and efficient photothermal therapy (PTT) of MRSA infections in mice. Remarkably, the SiO2-Cy-Van nanoprobes can also afford a long-term tracking (16 days) of the development of MRSA infections, allowing real-time estimation of bacterial load in infected tissues and further providing a possible way to monitor the efficacy of antimicrobial treatment. The strategy of bacteria-activated polyelectrolyte dissociation from nanoparticles proposed in this work could also be used as a general method for the design and fabrication of bacteria-responsive functional nanomaterials that offer possibilities to combat drug-resistant bacterial infections.
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TL;DR: The use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this, so the current research on nanoparticles and other nanomaterials are summarized.
Abstract: Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are enzyme inactivation, decreased cell permeability, target protection, target overproduction, altered target site/enzyme, increased efflux due to over-expression of efflux pumps, among others. Other more complex phenotypes, such as biofilm formation and quorum sensing do not appear as a result of the exposure of bacteria to antibiotics although, it is known that biofilm formation can be induced by antibiotics. These phenotypes are related to tolerance to antibiotics in bacteria. Different strategies, such as the use of nanostructured materials, are being developed to overcome these and other types of resistance. Nanostructured materials can be used to convey antimicrobials, to assist in the delivery of novel drugs or ultimately, possess antimicrobial activity by themselves. Additionally, nanoparticles (e.g., metallic, organic, carbon nanotubes, etc.) may circumvent drug resistance mechanisms in bacteria and, associated with their antimicrobial potential, inhibit biofilm formation or other important processes. Other strategies, including the combined use of plant-based antimicrobials and nanoparticles to overcome toxicity issues, are also being investigated. Coupling nanoparticles and natural-based antimicrobials (or other repurposed compounds) to inhibit the activity of bacterial efflux pumps; formation of biofilms; interference of quorum sensing; and possibly plasmid curing, are just some of the strategies to combat multidrug resistant bacteria. However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this. In this review, we will summarize the current research on nanoparticles and other nanomaterials and how these are or can be applied in the future to fight multidrug resistant bacteria.
533 citations
TL;DR: The light-activatable hydrogel-based platform allows us to release antibiotics more precisely, eliminate bacteria more effectively, and inhibit bacteria-induced infections more persistently, which will advance the development of novel antibacterial agents and strategies.
303 citations
TL;DR: P pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wound is reported based on the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH.
Abstract: Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.
233 citations
TL;DR: A comprehensive understanding of various PTAs is required for the better application of PTT in antibacterial treatment and the PTT-involved multifunctional theranostics nanoplatforms and the potential approaches for reducing the side effects are discussed.
229 citations
TL;DR: A hybrid polydopamine/Ag3PO4/graphene oxide (GO) coating is designed and constructed to achieve rapid bacteria killing and eliminate biofilms in situ and can maintain a repeatable and sustained antibacterial efficacy.
Abstract: Bacterial infection and associated complications are threats to human health especially when biofilms form on biomedical devices and artificial implants. Herein, a hybrid polydopamine (PDA)/Ag3PO4/graphene oxide (GO) coating is designed and constructed to achieve rapid bacteria killing and eliminate biofilms in situ. By varying the amount of GO in the hybrid coating, the bandgap can be tuned from 2.52 to 2.0 eV so that irradiation with 660 nm visible light produces bacteria-killing effects synergistically in concert with reactive oxygen species (ROS). GO regulates the release rate of Ag+ to minimize the cytotoxicity while maintaining high antimicrobial activity, and a smaller particle size enhances the yield of ROS. After irradiation with 660 nm visible light for 15 min, the antimicrobial rates of the PDA/Ag3PO4/GO hybrid coating against Escherichia coli and Staphylococcus aureus are 99.53% and 99.66%, respectively. In addition, this hybrid coating can maintain a repeatable and sustained antibacterial eff...
218 citations
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Abstract: The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance--the legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs.
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DSM1
TL;DR: It is demonstrated that tissue distribution of gold nanoparticles is size-dependent with the smallest 10nm nanoparticles showing the most widespread organ distribution.
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TL;DR: It is believed these newly developed multifunctional NIR dyes will broaden current concept of tumor targeted imaging and hold promise to make an important contribution to the diagnosis and therapeutics for the treatment of cancer.
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TL;DR: This critical review provides an overview on the formation of pi-stacks of functional dyes in solution, aiming to acquaint young researchers with this topical research field and to stimulate further advance in supramolecular dye chemistry.
Abstract: This critical review provides an overview on the formation of π-stacks of functional dyes in solution, aiming to acquaint young researchers with this topical research field and to stimulate further advance in supramolecular dye chemistry. Different mathematical models that have been proposed and applied for the description of aggregation equilibria of π-systems in solution are discussed. The factors that have significant impact on the structural features of aggregates and the thermodynamics of π–π stacking such as electrostatic interactions, size and geometry of the dye molecules are covered in this review. A comparison of the binding strength is made for different classes of functional π-conjugated systems, from simple benzene to more extended polycyclic hydrocarbon molecules, including triphenylenes and hexabenzocoronenes, heteroaromatic porphyrins and phthalocyanines, quadrupolar naphthalene and perylene bisimides, dipolar or even zwitterionic merocyanines and squaraines, and some macrocyclic dyes. Solvent effects on binding constants are analysed by linear free energy relationships with various solvent polarity scales (98 references with multiple entries).
852 citations
TL;DR: A strong structure–activity relationship was observed as a function of AuNP functionality, providing guidance to activity prediction and rational design of effective antimicrobial nanoparticles.
Abstract: We present the use of functionalized gold nanoparticles (AuNPs) to combat multi-drug-resistant pathogenic bacteria. Tuning of the functional groups on the nanoparticle surface provided gold nanoparticles that were effective against both Gram-negative and Gram-positive uropathogens, including multi-drug-resistant pathogens. These AuNPs exhibited low toxicity to mammalian cells, and bacterial resistance was not observed after 20 generations. A strong structure–activity relationship was observed as a function of AuNP functionality, providing guidance to activity prediction and rational design of effective antimicrobial nanoparticles.
583 citations