Design of polyethylene glycol–polyethylenimine nanocomplexes as non‐viral carriers: mir‐150 delivery to chronic myeloid leukemia cells

Abstract

MicroRNAs (miRNAs) are acknowledged as indispensable regulators relevant in many biological processes, and they have been pioneered as therapeutic targets for curing disease. miRNAs are single-stranded, small (19-22 nt) regulatory non-coding RNAs whose deregulation of expression triggers human cancers, including leukemias, mainly through dysregulation of expression of leukemia genes. miRNAs can function as tumour suppressors (suppressing malignant potential) or oncogenes (activating malignant potential) like actors of complex diseases. To address the issue of overcoming instability and low transfection efficiency in vitro, the polyethylene glycol-polyethyleneimine (PEG-PEI) nanoparticle was used as non-viral vector carrier for miR-150 transfection, which is downregulated in chronic myeloid leukemia. PEG-PEI [PEG(550)3 -g-PEI(1800) ]/miRNA nanocomplexes were synthesised and characterised by particle size distribution (PSD), polydispersity index (PDI) and zeta potential, surface charge, their cytotoxicity, and transfection efficiency. Interaction with human leukemia cells (K-562 and KU812) and control cells NCI-BL2347 with them has been investigated. The transfection efficiency of PEG-PEI/miRNA at N/P 26 rose 6.7-fold above the control by qRT-PCR. The size of homogenous nanocomplexes (PBI < 0.5) was 160.8 ± 11 nm. The data indicate that PEG-PEI may be an encouraging non-viral carrier for altering miRNA expression in the treatment of chronic myeloid leukemia, with many advantages such as relatively high miRNA transfection efficiency and low cytotoxicity.

Identification of MLL-fusion/MYC⊣miR-26⊣TET1 signaling circuit in MLL-rearranged leukemia

“…Various types of nanoparticles have been developed to deliver miRNA oligos to target leukemic cells (e.g. [77–79]). Thus, employing miR-26a-based nanoparticles, alone or in combination with other therapeutic agents, may represent an effective novel therapeutic strategy to treat MLL -rearranged AML, a type of dismal cancer that is resistant to contemporary therapies.…”

E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis

“…Efficient tissue-specific delivery of therapeutic miRs in vivo is a major challenge for miR-based therapy 11 . Nanoparticles have emerged as a promising vector for miR delivery 12 , and polyethylene glycol-polyethyleneimine (PEG/PEI) nanoparticles have been validated as an efficient delivery vector 13 . However, rapid clearance and poor targeting limit their clinical value.…”

MicroRNAs as mediators of cardiovascular disease: Targets to be manipulated

“…Furthermore, optimized means of effective miRNA delivery to target tissues or organs are yet to be developed. Although a number of different approaches to facilitate effective miRNA delivery, such as nanotechnology-based [23] , lipidbased [24] , and virus-based miRNA delivery systems [25] , have been designed, there still remains issue of toxicity which often led to ultimate death of animals and target specific delivery [26,27] . Thus, as contingency strategy, it may be necessary to start to find means of regulating specific miRNAs in situ other than delivering exogenous miRNAs to effectively utilize miRNAs as potent therapeutic target for treating diseases.…”