Polymeric microspheres as stabilizing anchors for oligonucleotide delivery to dendritic cells.
The aim of this study is to evaluate a novel microspheric vector for delivery of oligonucleotides (ODN) into dendritic cells (DC). A requirement of decoy-based modulation of transcriptional activities in DC is that the ODN would have to accumulate inside the cell. Using an ex vivo DC culture model, we demonstrate that anionic microspheres (MS) coated with an ornithine/histadine-based cationic peptide (O10H6) is an effective carrier of short ODN. This method does not disrupt the colloidal nature of the microspheric particles. The MS provide stabilizing effect on DNA and O10H6 complexation. Accumulation of ODN in DC is greatly enhanced with the surface modified MS. Taken together, these data demonstrate that the self assembly system of MS(O10H6) is an effective delivery vehicle for DNA-based modulation of DC functions.
Kovacs
Jeffrey R
JR
Division of Pharmaceutical Sciences, Duquesne University, Mellon Hall 413, 600 Forbes Avenue, Pittsburgh, PA 15282, USA.
Zheng
Ying
Y
Shen
Hongmei
H
Meng
Wilson S
WS
D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis; D002412:Cations; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D018014:Gene Transfer Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008863:Microspheres; D009841:Oligonucleotides / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014158:Transcription, Genetic
D039521:CD11c Antigen; D002412:Cations; D009841:Oligonucleotides; D011108:Polymers; D004247:DNA; D016650:Fluorescein-5-isothiocyanate