To satisfy the ever-growing demand in bacterial infection therapy and other fields of science, great effort is being devoted to the development of methods to precisely control drug release and achieve targeted use of an active substance at the right time and place. Here, a new strategy for bacterial infection combination therapy based on the light-responsive zeolitic imidazolate framework (ZIF) is reported. A pH-jump reagent is modified into the porous structure of ZIF nanoparticles as a gatekeeper, allowing the UV-light (365 nm) responsive in situ production of acid, which subsequently induces pH-dependent degradation of ZIF and promotes the release of the antibiotic loaded in the mesopores. The combination of the UV-light, the pH-triggered precise antibiotic release, and the zinc ions enables the light-activated nanocomposite to significantly inhibit bacteria-induced wound infection and accelerate wound healing, indicating a switchable and synergistic antibacterial effect. The light irradiated accumulation of acid ensures the controlled release of antibiotic and controlled degradation of ZIF, suggesting the therapeutic potential of the metal-organic frameworks-based smart platform for controlling bacterial infection.
The development of novel antimicrobial agents is a top priority in the fight against drug-resistant bacteria.Here, we synthesized a green nanoantibiotic, nitrogen-doped carbon quantum dots (N-CQDs) from bis-quaternary ammonium salt (BQAS) as carbon and nitrogen sources. The as-obtained N-CQDs possess high antibacterial activity (>99%) against both methicillin-resistant Staphylococcus aureus (MRSA) and Ampicillin-resistant Escherichia coli bacteria in vitro than some known clinical antibiotics (vancomycin and gentamicin). The N-CQDs can kill MRSA pathogens without inducing resistance, prevent biofilm formation and eliminate established biofilm and persister cells. The treatment of N-CQDs can significantly reduce the amount of bacteria on the infected tissue and accelerate wound healing. The N-CQDs are positively charged, thus enabling them to interact with bacterial cell membrane through electrostatic interaction, leading to severe damage and an increased permeability of the cell membrane, which further promotes the penetration of N-CQDs into the membrane and induces the degradation of DNA by N-CQDs generated reactive oxygen species. The N-CQDs also play a role in obstructing the intracellular metabolic pathways of MRSA. The overall data demonstrate the green nanoantibiotic as an excellent eradicator of biofilm and persister cells as well as a promising antibacterial candidate for treating infections induced by drug-resistant bacteria.
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 (CaO 2) 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 CaO 2 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.
The development of new antibacterial agents to deal with the emergence and spread of antibiotic resistance in Gram-positive bacterial pathogens has become an increasing problem. Here, a new strategy is developed for the effective targeting and killing of Gram-positive bacteria based on vancomycin (Van)-modified gold nanostars (AuNSs). Our work has demonstrated that the Van-modified AuNSs (AuNSs@Van) can not only selectively recognize methicillin-resistant Staphylococcus aureus (MRSA) but also kill MRSA under near-infrared laser irradiation in vitro. Additionally, AuNSs@Van shows satisfactory biocompatibility and antibacterial activity in treating bacterial infection in vivo. The attractive trait of AuNSs@Van is attributed to the physical effect of its antibacterial activity, with less potential for resistance development. The aforementioned advantages indicate the potential of AuNSs@Van as a photothermal antibacterial agent for effectively combating Gram-positive bacteria in the field of health care.
Helicobacter pylori (H. pylori) infection has ≈75% probability of causing gastric cancer, so it is considered to be the strongest single risk factor for gastric malignancies. However, the harsh gastric acid environment has created obstacles to medical treatment. This work reports a nanomotor with a bottle‐shaped container that can be loaded with small molecules of clarithromycin, nano calcium peroxide (CaO2), and Pt nanoparticles (Pt NPs) by ultrasound. Nanomotors can quickly consume gastric acid through the chemical reaction of CaO2 to temporarily neutralize gastric acid. The product hydrogen peroxide (H2O2) is catalytically decomposed into a large amount of oxygen (O2) by Pt NPs. The local concentration gradient of O2 bubbles causes it to be expelled from the nanobottles through a narrow opening, and then push the nanobottles forward to provide maximum release and prodrug efficacy. Experiments in animal models show that 15 mg nanomotors can safely and quickly neutralize gastric acid in the stomach and simultaneously release prodrugs to achieve good therapeutic effects without causing acute toxicity. H. pylori burden in mice was 2.6 orders of magnitude lower than that in the control group. The stomach returns to normal pH within 1 d after administration.
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