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WIREs Nanomed Nanobiotechnol
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Nanomaterials with active targeting as advanced antimicrobials

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Abstract With a growing health threat of bacterial resistance to antibiotics, the nanomaterials have been extensively studied as an alternative. It is assumed that antimicrobial nanomaterials can affect bacteria by several mechanisms simultaneously and thereby overcome antibiotic resistance. Another promising potential use is employing nanomaterials as nanocarriers for antibiotics in order to overcome bacterial defense mechanisms. The passive targeting of nanomaterials is the often used strategy for bacterial treatment, including intracellular infections of macrophages. Furthermore, the specific targeting enhances the efficacy of antimicrobials and reduces side effects. This review aims to discuss advantages, disadvantages, and challenges of nanomaterials in the context of the targeting strategies for antimicrobials as advanced tools for treatments of bacterial infections. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
Effect of nanocarriers and inherent antibacterial nanoparticles on resistant Gram‐negative bacteria. (a) Nanocarrier with encapsulated antibiotic penetrates to the cell. Modified particle overcomes the resistant system by encapsulation of antibiotic. Bacterial cell is not able to detect the antibiotic presence in the environment and thus permits its penetration into the cell. Modified hydrophobic layer of nanocarrier helps the influx of antibiotic into the hydrophobic outer lipopolysaccharide membrane of Gram‐negative cell wall, especially into their resistant forms. (b) Antibacterial effect of inherent antibacterial nanoparticles is caused by their accumulation on the cell‐wall surface and penetration into the cell where they generate ROS, alter membrane permeability, and/or damage DNA. ROS, reactive oxygen species
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The AuNC loaded by daptomycin (active against MRSA) is conjugated with antibodies aSpA against staphylococcal protein A. The targeted nanodrug is activated by near‐infrared light and thermal energy is created. The activated temperature change leads to controlled antibiotic release. Reprinted and published with permission from Meeker et al. (2016). AuNC, gold nanocages; MRSA, methicillin‐resistant Staphylococcus aureus
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(Top) Over the surface of PLGA NPs loaded by antibiotics the derived extracellular vesicle membrane (EV ghost) of S. aureus is coated. (Bottom) The infected macrophage presents antigens to the same pathogen on its surface, because of fast pathogen detection and removal. The NPs are camouflaged with the S. aureus membrane proteins, which interacts with macrophage. The camouflaged NPs are considered as pathogen and consequently are internalized inside the host cell and the cargo (antibiotics) is released. Reprinted and published with permission from Gao et al. (2019). NPs, nanoparticles; PLGA, poly(lactic‐co‐glycolic acid)
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The model of antimicrobial effect of pβCD in lungs (alveoli) infected by M. tuberculosis. (a) M. tuberculosis invade alveolar macrophages through membrane cholesterol and replicates inside macrophages. (b) pβCDs with encapsulated antibiotics release the drug directly inside macrophages and kill intracellular M. tuberculosis (c) The pβCD presence also induce apoptosis of host cell, when bacteria is killed trough efferocytosis. (d) The bacterial uptake is hindered by depletion of membrane cholesterol. Reprinted and published with permission from Machelart et al. (2019). pβCD, poly‐beta‐cyclodextrins
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Various options of NPs functionalization for active targeting strategy. NPs, nanoparticles
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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