Mannosylated biodegradable polyethyleneimine for targeted DNA delivery to dendritic cells. 2012

Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
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

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.

UI MeSH Term Description Entries
D008297 Male Males
D008358 Mannose A hexose or fermentable monosaccharide and isomer of glucose from manna, the ash Fraxinus ornus and related plants. (From Grant & Hackh's Chemical Dictionary, 5th ed & Random House Unabridged Dictionary, 2d ed) D-Mannose,Mannopyranose,Mannopyranoside,D Mannose
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D011094 Polyethyleneimine Strongly cationic polymer that binds to certain proteins; used as a marker in immunology, to precipitate and purify enzymes and lipids. Synonyms: aziridine polymer; Epamine; Epomine; ethylenimine polymer; Montrek; PEI; Polymin(e). Polyaziridine,Polyethylenimine,Polyaziridines,Polyethyleneimines,Polyethylenimines
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA

Related Publications

Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
June 2012, Bioconjugate chemistry,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
June 2006, The Journal of pharmacy and pharmacology,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
July 2019, Journal of biomedical nanotechnology,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
April 2015, Journal of nanobiotechnology,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
January 2012, International journal of nanomedicine,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
January 2010, Methods in molecular biology (Clifton, N.J.),
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
March 2012, Biomacromolecules,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
July 1999, The Journal of biological chemistry,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
November 2005, Biomaterials,
Xun Sun, and Simu Chen, and Jianfeng Han, and Zhirong Zhang
January 2012, Journal of nanoscience and nanotechnology,
Copied contents to your clipboard!