Methods for assembling B-cell lymphoma specific and internalizing aptamer-siRNA nanoparticles via the sticky bridge.

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.