title: PH-sensitive self-assembled carboxymethyl chitosan-modified DNA/polyethylenimine complexes for efficient gene delivery.
abstract: In this study, DNA/polyethylenimine/carboxymethy chitosan ternary complexes (DPCs) were developed as a pH-sensitive gene delivery system via a layer-by-layer self-assembly technique. The DPCs assumed an obvious layered structure and showed good DNA-condensation ability. The result of a DNase I protection assay indicated that DPCs could effectively protect DNA from being degraded by nucleases. Compared with DNA/polyethylenimine binary complexes (DPs), DPCs showed better stability in plasma and lower cytotoxicity and acute toxicity due to carboxymethyl chitosan (CMCS) modification. The results of a pH-sensitive experiment confirmed that the outermost CMCS layer of the DPCs could peel off in an acidic environment (pH 6.5) due to the pH sensitivity of CMCS. In vitro transfection results showed that DPCs have good transfection ability under conditions that mimicked a tumor's pH environment, which also indicated that CMCS could detach from the DPCs in response to the acidic environment of tumor tissue. These results showed that CMCS modification could endow DPCs with good stability and low toxicity without inhibiting transfection efficiency. In conclusion, DPCs have the advantages of long circulation, good safety, pH sensitivity and ease of construction, which might provide a promising approach for efficient gene delivery.
authors.forename: Fengxi
authors.initials: F
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D004058:Diffusion; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000235:genetics*; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D053769:Nanocapsules; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan