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Mannosylated Polyethyleneimine-Hyaluronan Nanohybrids for Targeted Gene Delivery to Macrophage-Like Cell Lines

ARAN - Access to Research at NUI Galway

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dc.contributor.author Mahor, Sunil
dc.contributor.author Dash, Biraja C.
dc.contributor.author O'Connor, Stephen
dc.contributor.author Pandit, Abhay
dc.date.accessioned 2012-10-24T11:14:19Z
dc.date.available 2012-10-24T11:14:19Z
dc.date.issued 2012-05-02
dc.identifier.citation Mahor, S,Dash, BC,O'Connor, S,Pandit, A (2012) 'Mannosylated Polyethyleneimine-Hyaluronan Nanohybrids for Targeted Gene Delivery to Macrophage-Like Cell Lines'. Bioconjugate Chemistry, 23 :1138-1148. en_US
dc.identifier.issn 1138¿1148
dc.identifier.uri http://hdl.handle.net/10379/3008
dc.description Journal article en_US
dc.description.abstract Nonviral gene delivery systems have a number of limitations including low transfection efficiency, specificity, and cytotoxicity, especially when the target cells are macrophages. To address these issues, the hypothesis tested in this study was that mannose functionalized nanohybrids composed of synthetic and natural polymers will improve transfection efficiency, cell viability, and cell specificity in macrophages. Robust nanohybrids were designed from hyaluronic acid (HA) and branched polyethyleneimine (bPEI) using carbodiimide chemistry. The reaction product, i.e., branched polyethyleneimine-hyaluronic acid (bPEI-HA) copolymer was subsequently functionalized with mannose at the terminal end of the copolymer to obtain mannosylated-bPEI-HA (Man-bPEI-HA) copolymer. UV spectroscopy and gel retardation studies confirmed the formation of polyplexes at polymer to DNA weight ratio >= 2. Alamar Blue and MTT assay revealed that the cytotoxicity of the developed nanohybrids were significantly (P < 0.05) lower than that of unmodified bPEI. Mannose functionalization of these nanohybrids showed specificity for both murine and human macrophage-like cell lines RAW 264.7 and human acute monocytic leukemia cell line (THP1), respectively, with a significant level (P < 0.05) of expression of gaussia luciferase (GLuc) and green fluorescent reporter plasmids. Internalization studies indicate that a mannose mediated endocytic pathway is responsible for this higher transfection rate. These results suggest that hyaluronan-based mannosylated nanohybrids could be used as efficient carriers for targeted gene delivery to macrophages. en_US
dc.language.iso en en_US
dc.publisher American Chemical Society en_US
dc.relation.ispartof Bioconjugate Chemistry en
dc.subject Low molecular weight en_US
dc.subject Receptor-mediated endocytosis en_US
dc.subject Transfection efficiency en_US
dc.subject In-vivo en_US
dc.subject Mannose receptor en_US
dc.subject Human glucocerebrosidase en_US
dc.subject Intracellular delivery en_US
dc.subject Alveolar macrophages en_US
dc.subject Antigen presentation en_US
dc.subject Blood compatibility en_US
dc.title Mannosylated Polyethyleneimine-Hyaluronan Nanohybrids for Targeted Gene Delivery to Macrophage-Like Cell Lines en_US
dc.type Article en_US
dc.date.updated 2012-10-18T16:57:20Z
dc.identifier.doi DOI 10.1021/bc200599k
dc.local.publishedsource http://dx.doi.org/10.1021/bc200599k en_US
dc.description.peer-reviewed peer-reviewed
dc.contributor.funder |~|
dc.internal.rssid 2194444
dc.local.contact Abhay Shashikant Pandit, Mechanical & Biomedical Eng, College Of Eng & Informatics, Room 304, Nfb Building, Ida Bus Park, Dangan, Nui Galway. 2758 Email: abhay.pandit@oegaillimh.ie
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