title: Mannosylated biodegradable polyethyleneimine for targeted DNA delivery to dendritic cells.
abstract: BACKGROUND
  To establish a potential gene-delivery system with the ability to deliver plasmid DNA to dendritic cells (DCs) more efficiently and specifically, we designed and synthesized a low-molecular-weight polyethyleneimine and triethyleneglycol polymer (PEI-TEG) and a series of its mannosylated derivatives.
  
  
  METHODS
  PEI-TEG was synthesized from PEI2000 and PEI600 with TEG as the cross-linker. PEI-TEG was then linked to mannose via a phenylisothiocyanate bridge to obtain man-PEI-TEG conjugates. The DNA conveyance abilities of PEI-TEG, man-PEI-TEG, as well as control PEI25k were evaluated by measuring their zeta potential, particle size, and DNA-binding abilities. The in vitro cytotoxicity, cell uptake, and transfection efficiency of these PEI/DNA complexes were examined on the DC2.4 cell line. Finally, a maturation experiment evaluated the effect of costimulatory molecules CD40, CD80, and CD86 on murine bone marrow-derived DCs (BMDCs) using flow cytometry.
  
  
  RESULTS
  PEI-TEG and man-PEI-TEG were successfully synthesized and were shown to retain the excellent properties of PEI25k for condensing DNA. Compared with PEI-TEG as well as PEI25k, the man-PEI-TEG had less cytotoxicity and performed better in both cellular uptake and transfection assays in vitro. The results of the maturation experiment showed that all the PEI/DNA complexes induced an adequate upregulation of surface markers for DC maturation.
  
  
  CONCLUSIONS
  These results demonstrated that man-PEI-TEG can be employed as a DC-targeting gene-delivery system.
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China. xunsun22@gmail.com
authors: Xun
authors: X
authors: Sun
authors: Simu
authors: S
authors: Chen
authors: Jianfeng
authors: J
authors: Han
authors: Zhirong
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D005434:Flow Cytometry; D008297:Male; D008358:Mannose / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D005026:Ethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D008358:Mannose