title: Methods for assembling B-cell lymphoma specific and internalizing aptamer-siRNA nanoparticles via the sticky bridge.
abstract: Structured functional RNA entities, including aptamers and siRNAs, have amazing versatility in structure and function. These molecules can serve as powerful, attractive building blocks for the bottom-up assembly of complex nanostructures. Here, we describe novel cell-type specific and internalizing B-cell activating factor receptor (BAFF-R) aptamer-siRNA delivery systems for B-cell lymphoma therapy, in which both the aptamer and the Dicer substrate siRNA (DsiRNA) portions are conjugated through a "sticky bridge." The BAFF-R is overexpressed on the surface of B-cell malignancies, allowing binding and internalization of the aptamer-stick-siRNA nanoparticles. STAT3 siRNAs are encapsulated within the nanoparticles delivered by the BAFF-R aptamers and are localized to the cytoplasm, resulting in robust gene silencing of STAT3 mRNAs in a variety of B-cell lines. Moreover, these nanoparticles do not induce cell proliferation and apoptosis. Collectively, aptamer-mediated delivery strategies provide a toolset to become a more widely used therapeutic modality for the treatment of diseases.
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA, USA.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Zhou
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
authors.forename: Ka To
authors.initials: KT
authors.lastname: Shum
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics* / Q000627:therapeutic use; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D020868:Gene Silencing; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000628:therapy; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D036103:Nanotechnology / Q000379:methods*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D052157:Aptamers, Nucleotide; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human