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Tocopheryl oligochitosan-based self assembling oligomersomes for siRNA delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
7590 557 2011 9 PDF Available
Title
Tocopheryl oligochitosan-based self assembling oligomersomes for siRNA delivery
Abstract

Amphiphilic α-tocopherol oligochitosan conjugates were constructed by conjugating α-tocopherol succinate to water soluble oligochitosans with various molecular weights. In aqueous medium, the tocopherol oligochitosan conjugates self-assembled to single layered oligomersomes. The sizes of α-tocopherol-oligochitosan-based oligomersomes (TCOsomes) could be controlled by chain lengths of oligochitosans. The mean sizes of TCOsomes were 220 and 377 nm as the sizes of oligochitosans were 4000 and 12,500, respectively. For all TCOsomes formed in this study, polydispersity indexes were in the ranges of 0.111–0.256. Cryo-TEM images showed clear thickening in the unilamellar layer of TCOsomes upon complexation with siRNAs. Zeta potentials decreased as the ratios of siRNA/TCOsomes increased. TCOsomes self-assembled from tocopherol-oligochitosan 4K (TCOsome4K) significantly enhanced the cellular uptake of siRNAs (>98%), and reduced the expression of target proteins more effectively than did Lipofectamine 2000. In tumor xenografted mice, the intratumoral administration of siMcl-1 using TCOsomes substantially silenced the expression of Mcl-1 and prevented the growth of tumor. The hematoxylin-eosin staining showed the apoptosis of cells in the tissues of the mice treated with siMcl-1/TCOsome4K complexes, but not with siGL2/TCOsome4K complexes. The self-assembling and size-controllable oligomersomes might be suitable for effective in vivo delivery of siRNAs.

Keywords
Self-assembling; Tocopherol; Oligochitosan; Oligomersomes; siRNA delivery
First Page Preview
Tocopheryl oligochitosan-based self assembling oligomersomes for siRNA delivery
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 3, January 2011, Pages 849–857
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering