Journal
JOURNAL OF DRUG TARGETING
Volume 9, Issue 2, Pages 123-+Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10611860108997923
Keywords
folic acid; endocytosis; gene expression; IFN-gamma; luciferase; polyethylenimine
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Folate-polyethylene glycol-folate-grafted-polyethylenimine (FPF-g-PEI), was synthesized by linking folic acid to both ends of a mono-functional PEG and then grafting to PEI. The graft ratio was determined using Beer's law by measuring the UV absorbance at 363 nm. The pH profile, diameter and shape of the carriers were determined. Transfection efficiencies were optimized in normal smooth muscle cells (SMC) and CT 26 colon adenocarcinoma cells using plasmid DNA encoding luciferase reporter gene. Free folic acid was shown to inhibit transfection with FPF-2.3g-PEI at neutral charge ratio. Relative toxicity between PEI and the modified carrier was measured using MTT colorimetric assay. Therapeutic potential of pmIFN-gamma complexed with these polymeric carriers in terms of gene expression was determined at protein and mRNA levels using ELISA and RT PCR. FPF-g-PEI was determined to have 2.3 folate-PEG-folate (FPF) linear polymers grafted to each PEI molecule. The average molecular weight was measured to be similar to 33,500 Mw and the pH profile was characteristic of endosomal disruption capacity. Atomic Force Microscopy (AFM) and Dynamic Laser Light Scattering (DLLS) indicated FPF-2.3g-PEI and PEI (at 2 w/w ratio) efficiently condensed plasmid DNA resulting in oblique spheroid polyplexes with a mean diameter of similar to 150 nm. FPF-2.3g-PEI was superior to PEI in terms of cytotoxicity and transfection efficiency in cancer cells. Smooth muscle cells showed no specificity for folate tethered complexes, where PEI/pLuc complexes yielded higher efficiencies.
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