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dc.contributor.authorMahor, Sunil
dc.contributor.authorDash, Biraja C.
dc.contributor.authorO'Connor, Stephen
dc.contributor.authorPandit, Abhay
dc.identifier.citationMahor, 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.descriptionJournal articleen_US
dc.description.abstractNonviral 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.publisherAmerican Chemical Societyen_US
dc.relation.ispartofBioconjugate Chemistryen
dc.subjectLow molecular weighten_US
dc.subjectReceptor-mediated endocytosisen_US
dc.subjectTransfection efficiencyen_US
dc.subjectMannose receptoren_US
dc.subjectHuman glucocerebrosidaseen_US
dc.subjectIntracellular deliveryen_US
dc.subjectAlveolar macrophagesen_US
dc.subjectAntigen presentationen_US
dc.subjectBlood compatibilityen_US
dc.titleMannosylated Polyethyleneimine-Hyaluronan Nanohybrids for Targeted Gene Delivery to Macrophage-Like Cell Linesen_US
dc.identifier.doiDOI 10.1021/bc200599k
dc.local.contactAbhay Shashikant Pandit, Mechanical & Biomedical Eng, College Of Eng & Informatics, Room 304, Nfb Building, Ida Bus Park, Dangan, Nui Galway. 2758 Email:

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