Controlled dendrimersome nanoreactor system for localised hypochlorite-induced killing of bacteria
| Autor: | Lucia Massi, Valeria Nele, Anna Klöckner, Andrew M. Edwards, Adrian Najer, Junyi Che, Michael Potter, Catherine A. Saunders, Shaodong Zhang, Jelle Penders, James Doutch, Oscar Ces, Margaret N. Holme, Molly M. Stevens |
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| Přispěvatelé: | Wellcome Trust, Engineering and Physical Sciences Research Council, Commission of the European Communities |
| Rok vydání: | 2020 |
| Předmět: |
Technology
semipermeable Chemistry Multidisciplinary General Physics and Astronomy Hypochlorite 02 engineering and technology Nanoreactor medicine.disease_cause MEMBRANES 01 natural sciences chemistry.chemical_compound General Materials Science dendrimersome Liposome biology Chemistry Chemistry Physical General Engineering MYELOPEROXIDASE 021001 nanoscience & nanotechnology Antimicrobial POLYMER NANOREACTORS toxin-activation Staphylococcus aureus Myeloperoxidase Physical Sciences Science & Technology - Other Topics 0210 nano-technology ENZYMES SURFACE Materials Science Materials Science Multidisciplinary 010402 general chemistry Article bactericidal medicine Nanoscience & Nanotechnology GLYCODENDRIMERSOMES Science & Technology MODULAR SYNTHESIS JANUS-DENDRIMERS REACTIVITY 0104 chemical sciences cascade nanoreactor POLYION COMPLEX VESICLES Polymersome biology.protein Biophysics Nanocarriers |
| Zdroj: | ACS Nano |
| Popis: | Antibiotic resistance is a serious global health problem necessitating new bactericidal approaches such as nanomedicines. Dendrimersomes (DSs) have recently become a valuable alternative nanocarrier to polymersomes and liposomes due to their molecular definition and synthetic versatility. Despite this, their biomedical application is still in its infancy. Inspired by the localized antimicrobial function of neutrophil phagosomes and the versatility of DSs, a simple three-component DS-based nanoreactor with broad-spectrum bactericidal activity is presented. This was achieved by encapsulation of glucose oxidase (GOX) and myeloperoxidase (MPO) within DSs (GOX-MPO-DSs), self-assembled from an amphiphilic Janus dendrimer, that possesses a semipermeable membrane. By external addition of glucose to GOX-MPO-DS, the production of hypochlorite (-OCl), a highly potent antimicrobial, by the enzymatic cascade was demonstrated. This cascade nanoreactor yielded a potent bactericidal effect against two important multidrug resistant pathogens, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), not observed for H2O2 producing nanoreactors, GOX-DS. The production of highly reactive species such as -OCl represents a harsh bactericidal approach that could also be cytotoxic to mammalian cells. This necessitates the development of strategies for activating -OCl production in a localized manner in response to a bacterial stimulus. One option of locally releasing sufficient amounts of substrate using a bacterial trigger (released toxins) was demonstrated with lipidic glucose-loaded giant unilamellar vesicles (GUVs), envisioning, e.g., implant surface modification with nanoreactors and GUVs for localized production of bactericidal agents in the presence of bacterial growth. |
| Databáze: | OpenAIRE |
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