title: Cancer-specific gene silencing through therapeutic siRNA delivery with B vitamin-based nanoassembled low-molecular-weight hydrogelators.
abstract: This paper describes the synthesis, characterization, and in vitro and in vivo siRNA transfection ability of B vitamin-based cationic clickable bolaamphiphiles (VBs). Our VBs derived from vitamins B₂, B₃, B₅, B₆, and B₇ formed nanoassembled low-molecular-weight hydrogelators (LMWGs, vitagels). The vitagels VB2, VB6, and VB7 (derived from vitamins B₂, B₆, and B₇, respectively) facilitated delivery of small interfering RNAs (siRNA), efficiently silencing gene expression specifically into cancer cell lines; in addition, the LMWGs derived from vitamins B₃, B₅, and B₆ were biocompatible. An ex vivo study in a mouse model revealed that the siRNA delivered by the vitagel VB7 was located primarily at the site of the tumor. The gene silencing efficiency of vascular endothelial growth factor siRNA delivered by vitagels was dependent on the nature of the vitamin headgroup, the N/P ratio, and, interestingly, the hydrogelation properties of the VBs.
authors.affiliation: Department of Chemistry, ‡Department of Life Sciences, and §Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology , Pohang 790-784, Korea.
authors.forename: Sachin Prakash
authors.initials: SP
authors.lastname: Patil
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jyoti Ramesh
authors.initials: JR
authors.lastname: Jadhav
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Jeon
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
authors.forename: Byeang Hyean
authors.initials: BH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D045744:Cell Line, Tumor; D057930:Click Chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D014803:Vitamin B Complex / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D034741:RNA, Small Interfering; D014803:Vitamin B Complex