Investigating siRNA delivery to chronic myeloid leukemia K562 cells with lipophilic polymers for therapeutic BCR-ABL down-regulation

Polymeric nanoparticle-mediated silencing of CD44 receptor in CD34+ acute myeloid leukemia cells

“…Lipid-modified polyethylenimines (PEIs) were synthesized using a modification of previously published procedures [34,39]. Caprylic acid (CA) and linoleic acid (LA) were used as the specific lipids for N-acylation of 2 kDa PEI (PEI2; purified by freezedrying of manufacturer-supplied product).…”

“…reverse-transcribed into cDNA as previously described [39]. Human beta-actin RNA (forward primer: 5 -CCA CCC CAC TTC TCT CTA AGG A-3 ; reverse primer: 5 -AAT TTA CAC GAA AGC AAT GCT ATC A-3 , IDT) was used as an internal control to evaluate transcripts for CD44s (forward primer: 5 -GGC CTT GGC TTT GAT TCT TG-3 ; reverse primer: 5 -CCA CTT GGC TTT CTG TCC T-3 , IDT).…”

“…In fact, siRNA silencing in LSPC has been shown to be the most challenging [38], making siRNA-mediated anti-CD44 approaches a difficult therapeutic modality. To overcome this limitation, we recently developed functional lipid-substituted polymeric materials that could efficiently deliver siRNA in both adherent breast cancer cells and leukemic cells grown in suspension [25][26][27]34,39]. We pursued silencing of various model (e.g., GFP) and targets (e.g., CXCR4, BCR-ABL) in differentiated types of AML and CML cell lines [34,39].…”

“…To overcome this limitation, we recently developed functional lipid-substituted polymeric materials that could efficiently deliver siRNA in both adherent breast cancer cells and leukemic cells grown in suspension [25][26][27]34,39]. We pursued silencing of various model (e.g., GFP) and targets (e.g., CXCR4, BCR-ABL) in differentiated types of AML and CML cell lines [34,39]. Importantly, we observed that cellular delivery of siRNA was dependent on the nature of lipid substituent, the extent of lipid substitution, and varied among the different AML cell lines as well as CML cell lines.…”

A novel peptide for efficient siRNA delivery in vitro and therapeutics in vivo

“…39 Ó 2015 Published by Elsevier Ltd. on behalf of Acta Materialia Inc. 40 41 42 43 1. Introduction 44 Since the discovery of RNA interference (RNAi), small interfer- 45 ing RNA (siRNA) has been considered a powerful tool to suppress 46 specific genes, and it shows great potential as an efficient thera- 47 peutic agent for many diseases, including cancer [1], HIV [2,3], 48 influenza [4], and others [5][6][7]. Consisting of 21-23 nucleotides, 49 double stranded siRNA molecules can bind to and degrade target 50 mRNA with complementary sequences [8].…”