siRNA Delivery Improvement by Co-formulation of Different Modified Polymers in Erythroleukemic Cell Line K562

摘要

>Objective(s): siRNA may be a very promising tool for treatment of various diseases especially in cancer therapy due to high specificity. One of the main hurdles applications of siRNAs in vivo is optimization of the delivery strategy, especially the carrier systems. The aim of this study was to optimize siRNA delivery into suspended erythroleukemic cell line K562. >Materials and Methods: We applied polyethyleneimine (PEI) and oligoethyleneimine (OEI) derivatives alone or their co-formulation with different agents such as chloroquine (a drug known to alter lysosomal pH and thus to inhibit lysosomal degradation of macromolecules), DOPE (lipophilic agent), succinic acid (introduction of negatively charged to polymer) and transferrin (the ligand of transferring receptor which is over-expressed in many types of tumors and hematopoietic cells). >Results: In this study it was shown that utilizing a combination of 70% OEI-HA10 (ten hexyl acrylate residues per one OEI chain) plus 30% of transferin-PEI with Luc-siRNA was highly effective for transfecting K562 cell. This co-formulation silenced luciferase activity up to 70% after short time without any significant inhibition in the luciferase activity in siCONTROL wells. >Conclusion: In conclusion, the combination of modified PEI with transferrin and OEI by hexyl acrylate may increase siRNA delivery and reduce toxicity in hematopoietic suspended cells.