Receptor-mediated gene delivery into antigen presenting cells using mannosylated chitosan/DNA nanoparticles.
Dendritic cells (DCs) are professional antigen presenting cells that induce, sustain, and regulate immune responses. Gene modification of DCs is of particular interest for immunotherapy of diseases where the immunes system has failed or is abnormally regulated, such as in cancer or autoimmune disease. Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic DNA. Among various non-viral vectors, chitosan is considered to be a good candidate for gene delivery system, however, lack of cell specificity and low transfection of chitosan need to be overcome prior to clinical use. In this study, mannosylated chitosan (MC) was prepared to induce the receptor-mediated endocytosis and targeting into antigen presenting cells (APCs), especially DCs having mannose receptors. MC showed great ability to form complexes with DNA and showed suitable physicochemical properties for gene delivery system. It had low cytotoxicity and exhibited much enhanced gene transfer efficiency on the macrophage cell line than chitosan itself. Also, MC/DNA complex was more efficient for transferring IL-12 gene into DCs rather than water-soluble chitosan (WSC)/DNA one, which resulted in better induction of INF-gamma from DCs. Therefore, MC is a promising gene delivery system for repeated administration to maintain sustained gene expression, thereby opening the possibility for immunotherapy.
Kim
Tae Hee
TH
School of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
Nah
Jae Woon
JW
Cho
Myung-Haing
MH
Park
Tae Gwan
TG
Cho
Chong Su
CS
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008358:Mannose / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D011956:Receptors, Cell Surface; D004247:DNA; D048271:Chitosan; D008358:Mannose