Enhanced uptake and siRNA-mediated knockdown of a biologically relevant gene using cyclodextrin polyrotaxane

Abstract

Cellular investigations confirm the ability of cyclodextrin polyrotaxane nanoplexes to deliver siRNA for down-regulating genes relevant to the pathogenesis of tuberculosis.

Plasma and Liver Protein Binding ofN-Acetylgalactosamine–Conjugated Small Interfering RNA

“…siRNA is hypothesized to exist as a "rigid rod" in solution due to the geometry of the dsRNA A-form helix (Kornyshev and Leikin, 2013;Kozielski et al, 2013;Dandekar et al, 2015). We recently obtained a crystal structure of siRNA-X confirming its linear geometry (R h 5 ;2.7-3 nm; manuscript in preparation), consistent with literature descriptions of unmodified dsRNA (;0.28-nm helical rise/base pair or R h ;2.9 nm for 21-mer siRNA).…”

Polysaccharide‐Based Controlled Release Systems for Therapeutics Delivery and Tissue Engineering: From Bench to Bedside

“…CD‐based PPRs are noncovalently interlocked supermolecular architectures that are comprised of linear polymer components (guests) and encircled by CD components (hosts), and they are advancing rapidly in the area of stimuli‐responsive materials due to their unique features . Using similar mechanisms, Dandekar et al developed a cationic α‐/β‐CD‐based polyrotaxane, which can condense nucleic acids into nanoplexes for in vitro gene delivery . The CD polyrotaxane was obtained by subsequent incubation of amine functionalized β‐CD and α‐CD with ionene‐6,10 polymer, as the CD rings were threaded over the polymer chain with temperature activated noncovalent interactions .…”

Synthesis of the anionic hydroxypropyl-β-cyclodextrin:poly(decamethylenephosphate) polyrotaxane and evaluation of its cholesterol efflux potential in Niemann–Pick C1 cells

“…Poly(decamethylene phosphate) 1 was chosen as the guest polymer, because it is less toxic (LC 50 = 900 μg/mL for HEPG2 cells) than the previously used cationic polymers. 57 It was obtained through oxidation of poly(decamethylene phosphite) 2. This was performed in three steps via the polymeric phosphoryl chloride 3 and polymeric phosphoryl imidazolide 4 intermediates as shown in Scheme 1.…”

“…Assembly of polyrotaxanes through subsequent threading of large and small rings was already shown to be practicable as reported previously. 57,63 The HP-β-CD polyrotaxane 6 could be isolated in nearly quantitative yield after sequential threading of HP-β-CD and α-CD onto polyphosphate 1 and removal of excess α-CD and HP-β-CD by ultrafiltration. The solubility of 6 in water is 160 mg/mL.…”