Original ArticleNanostructured glycopolymer augmented liposomes to elucidate carbohydrate-mediated targeting
Graphical Abstract
In this study, we employed reversible addition fragmentation chain transfer (RAFT) polymerization to synthesize neoglycopolymers, consisting of mannose- and galactose methacrylate-based monomers copolymerized with cholesterol methacrylate for use in functional liposome studies. We elucidate the carbohydrate receptor-targeting paradigm for nanoparticle binding and delivery in in vitro alveolar macrophage models and demonstrate specific receptor-mediated uptake in a manner dependent on carbohydrate receptor expression. These results establish a platform capable of probing endogenous carbohydrate receptor-mediated targeting via glycofunctional nanomaterials.
Section snippets
Methods
Materials were purchased from Sigma–Aldrich unless otherwise specified. 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (ammonium salt) (DSPE-mPEG(2000)) were purchased from Avanti Polar Lipids (Alabaster, AL, USA). Rhodamine B 1,2-Dihexadecanoyl-sn-Glycero-3-Phosphoethanolamine was purchased from Life Technologies (Grand Island, NY USA). 4,4′-Azobis(4-cyanovaleric acid) (V501) was obtained from Wako
CD206 & CD301 receptor expression in mouse primary macrophage cells and macrophage cell lines
Cell surface expression of two C-type lectins, mannose receptor (CD206) and galactose-type lectin (CD301), was investigated in primary macrophage cells and commonly used macrophage cell lines, including mouse alveolar macrophages (AMs), bone marrow derived macrophages (BMDMs), RAW264.7, and MH-S. Cells were cultured with or without 20 ng/ml IL-4. The expression of CD206 and CD301 was observed by flow cytometry (Figure 1) and represented as percent of cells in the population positive for receptor
Discussion
Alveolar macrophages play an important role in the phagocytic clearance of inhaled microorganisms in the distal airways and the alveoli10, 32, 33. The inability to clear persistent foreign stimuli and to repair cellular damage can result in chronic pulmonary disease29, 34. Under chronic inflammatory conditions, AMs undergo phenotypic changes representing alternative (M2) polarization and an overexpression of the macrophage mannose receptor of these cells occurs4, 29, 30. For these reasons,
Acknowledgements
We would like to thank Dr. Liguo Wang and Lige Tonggu for technical support with Cryo-EM imaging and Julia Swanson and Fiona Brown for assisting in carbohydrate monomer synthesis.
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Cited by (0)
The authors declare no competing financial interests.
This work was supported by the Defense Threat Reduction Agency [grant number HDTRA1-13-1-0047]; and by the National Science Foundation Graduate Research Fellowship [DGE-0718124 and DGE-1256082].
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These authors contributed equally to this work.