title: Folic Acid Linked Chondroitin Sulfate-Polyethyleneimine Copolymer Based Gene Delivery System.
abstract: In our previous study, chondroitin sulfate-polyethylenimine copolymers (CP) have been synthesized and confirmed as potential gene delivery vectors. Efficient gene transfection is realized by chondroitin sulfate (ChS) that promotes CD44- mediated endocytosis and enhances the cellular uptake of CP/pDNA polyplexes besides clathrin-mediated endocytosis. In this study, the CP was functionalized with a folic acid (FA) molecule. This ancillary ligand allows polyplexes to bind with folate receptors (FR) in addition to the CD44 receptor. We conjugated FA-linked polyethylene glycol (FA-PEG) onto CP (FPCP) for tumor targeting and also synthesized mPEG-CP (MPCP) for comparison. The in vitro cell tests of polymer/pDNA polyplexes were done in FR-expressed U87 and FR-deficient A549 cells. The polymers exhibited less cytotoxicity than PEI-10K as well as PEI-25K against U87 and A549 cells. The transfection efficiency of FPCP/pDNA was higher than those of MPCP/pDNA and CP/pDNA. The cellular uptake pathways of FPCP/pDNA were tested in the cells in the presence of different endocytic chemical inhibitors. The CD44-, folate-, and caveolae-mediated pathways are involved in internalization of FPCP/pDNA. Recognition of FPCP to those receptors on the tumor surface is beneficial for enhanced cellular uptake of FPCP/pDNA, resulting in higher transgene expression than CP/pDNA and MPCP/pDNA.
authors: Yu-Lun
authors: YL
authors: Lo
authors: Pei-Chi
authors: PC
authors: Lo
authors: Chien-Chih
authors: CC
authors: Chiu
authors: Li-Fang
authors: LF
authors: Wang
mesh_terms: D002809:Chondroitin Sulfates / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics*; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D003432:Cross-Linking Reagents; D058973:Folate Receptors, GPI-Anchored; D053769:Nanocapsules; D011094:Polyethyleneimine; D002809:Chondroitin Sulfates; D005492:Folic Acid