Počet záznamů: 1
Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics
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SYSNO ASEP 0507773 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics Tvůrce(i) Crooke, S. N. (US)
Schimer, Jiří (UOCHB-X) RID, ORCID
Raji, I. (US)
Wu, B. (US)
Oyelere, A. K. (US)
Finn, M. G. (US)Zdroj.dok. Molecular Pharmaceutics. - : American Chemical Society - ISSN 1543-8384
Roč. 16, č. 7 (2019), s. 2947-2955Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova macrophage ; macrolide ; virus-like particles ; azithromycin ; clarithromycin ; lung targeting Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology Způsob publikování Omezený přístup Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000474475400011 EID SCOPUS 85068190698 DOI 10.1021/acs.molpharmaceut.9b00180 Anotace Macrophage cells are present in high abundance in the lung to intercept invading microorganisms that gain access through airway mucosal surfaces. Several bacterial pathogens have evolved the capacity to evade the innate immune response by establishing infections within pulmonary macrophages upon phagocytosis, leading to prolonged disease. Macrolide antibiotics such as azithromycin and clarithromycin accumulate in phagocytic cells and have been shown to preferentially distribute in tissues where populations of these cells reside. We employed this class of molecules as targeting ligands to direct virus-like particles (VLPs) to lung-resident macrophages. VLP-macrolide conjugates showed enhanced uptake into RAW 264.7 macrophage cells in culture, with azithromycin displaying the greatest effect, distinct differences were also observed for different macrocycle structures and orientations on the particle surface. Activation of macrophage cells was stimulated by particle uptake toward an intermediate activation state, in contrast to previous reports using macrolide-functionalized gold nanorods that stimulated a cytotoxic macrophage response. Attached azithromycin was also able to direct VLPs to the lungs in mice, with significant accumulation within 2 h of systemic injection. These results suggest that this new class of bioconjugate could serve as an effective platform for intracellular drug delivery in the context of pulmonary infections. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2020 Elektronická adresa https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00180
Počet záznamů: 1