Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics

0507773 - ÚOCHB 2020 RIV US eng J - Článek v odborném periodiku
Crooke, S. N. - Schimer, Jiří - Raji, I. - Wu, B. - Oyelere, A. K. - Finn, M. G.
Lung Tissue Delivery of Virus-Like Particles Mediated by Macrolide Antibiotics.
Molecular Pharmaceutics. Roč. 16, č. 7 (2019), s. 2947-2955. ISSN 1543-8384. E-ISSN 1543-8392
Institucionální podpora: RVO:61388963
Klíčová slova: macrophage * macrolide * virus-like particles * azithromycin * clarithromycin * lung targeting
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.321, rok: 2019
Způsob publikování: Omezený přístup
https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00180

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.
Trvalý link: http://hdl.handle.net/11104/0298743