Rational Design of a siRNA Delivery System: ALOX5 and Cancer Stem Cells as Therapeutic Targets

摘要: The search for an ideal gene delivery system is a long and laborious process in which several factors from the first idea to final formulation, including main challenges, peaks troughs, should be deeply taken into consideration ensure adequate biological safety vivo efficacy endpoints. Arachidonate 5-lipoxygenase (ALOX5), crucial player related with cancer development particular stem cells malignancy. In this work we describe behind of small interfering RNA (siRNA) inhibit ALOX5 (CSC), as model target gene. We started by screening chitosan polyplexes, among different types complexation conditions. Due low silencing obtained, polyplexes were combined Pluronic®-based polymeric micelles recognized advantages regarding transfection. tested particles improve polyplexes. Nevertheless, limited transfection efficiency was still detected. well-established polyethyleneimine (PEI) cationic polymer used substitution chitosan, combination micelles, originating PEI-siRNA-Pluronic® systems. presence Pluronic® F127 formulation showed utmost importance because not only activity improved, but also PEI-associated toxicity clearly reduced. This, allowed increase amount PEI inside its overall efficacy. Indeed, PEI, N/P ratios preparation methods until optimal composed 10k branched-based at ratio 50 selected. This micelle presented technological properties, profile, efficacy, resulting high strong reduction invasion transformation capabilities cell subpopulation isolated MDA-MB-231 triple negative breast cells. [READ ARTICLE](https://precisionnanomedicine.com/article/6489)