The siRNAsome: A Cation Free and Versatile Nanostructure for siRNA and Drug Codelivery

Nanoparticles show great potential for drug delivery. However, suitable nanostructures capable of loading a range of drugs (including hydrophobic/hydrophilic small molecules or biomolecular agents) together with the codelivery of siRNAs that avoid the problem of cation‐associated cytotoxicity, are lacking. Herein, we report a novel, siRNA‐based vesicle (siRNAsome) nanostructure which consists of a hydrophilic siRNA shell, a thermal and intracellular reduction sensitive hydrophobic median layer, and an empty aqueous interior that meets this need. The siRNAsome can serve as a versatile nanostructure to load drug agents with divergent chemical properties, therapeutic proteins as well as codelivering immobilized siRNAs without transfection agents. Importantly, a particular advantage of our siRNAsome is that inherent thermal/reduction responsiveness enables it to control drug loading and release. We show that when siRNAsomes are loaded with the hydrophilic drug doxorubicin hydrochloride (Dox·HCl) and anti‐P‐glycoprotein (Pgp) siRNA (to target the Pgp drug exporter), synergistic therapeutic activity is achieved in multidrug resistant (MDR) cancer cells and tumor model.

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