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dc.contributorMorris, Viola B.-
dc.contributorSharma, Chandra P.-
dc.identifier.citationBIOMATERIALS. 32; 11; 3030-3041en_US
dc.description.abstractFolate receptor mediated gene targeting provides several advantages such as delivery of high concentration of gene at specific tumor sites including brain, lung, ovary, uterus and kidney where folate receptors are over expressed. In the present study for both systemic stability and tumor targeting ability, poly (ethylene glycol) folic acid (PEG FA) conjugate was coupled with an arginine modified oligo (alkylaminosiloxane) graft poly (ethyleneimine) having enhanced transfection efficiency compared to poly (ethyleneimine). The resultant polymer P(SiDAAr)5FP2 complexed pDNA effectively and showed protection against nuclease degradation. The PEG group provided improved blood compatibility and cell viability. Uniformly oriented arginine moiety helped to enhance cellular and nuclear localisation, which led to improved transfection. The polymer was capable of releasing pDNA at the nucleus and being cleared from the cell after its purpose. Transfection in presence of cellular uptake inhibitors showed multiple pathways for cellular uptake of the targeted polymer, out of which folate receptor mediated uptake was more prominent. The folate mediated cellular uptake of P(SiDAAr)5FP2 was then confirmed by flow cytometric evaluation. The high accumulation of targeted polymers in the tumor tissues of tumor bearing mice from 2nd hour onwards proved the active targeting effect of the polymer. Besides tumor accumulation, the material showed capability to diffuse through the vascular endothelium. This property is expected to be beneficial for brain targeting experiments. (C) 2010 Elsevier Ltd. All rights reserved.-
dc.subjectDrug Delivery-
dc.titleFolate mediated L-arginine modified oligo (alkylaminosiloxane) graft poly (ethyleneimine) for tumor targeted gene delivery-
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