Nanoparticles show great potential for drug delivery. However, suitable nanostructures capable of loading a range of drugs together with the co-delivery of siRNAs, which avoid the problem of cation-associated cytotoxicity, are lacking. Herein, we report an small interfering RNA (siRNA)-based vesicle (siRNAsome), 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 co-delivering immobilized siRNAs without transfection agents. Importantly, the inherent thermal/reduction-responsiveness enables controlled drug loading and release. When siRNAsomes are loaded with the hydrophilic drug doxorubicin hydrochloride and anti-P-glycoprotein siRNA, synergistic therapeutic activity is achieved in multidrug resistant cancer cells and a tumor model.
[1]Henan Univ, Sch Life Sci, Henan & Macquarie Univ Joint Ctr Biomed Innovat, Kaifeng 475004, Henan, Peoples R China;
[2]Macquarie Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Sydney, NSW, Australia;
[3]Henan Univ, Coll Chem & Chem Engn, Kaifeng 475004, Peoples R China;
[4]Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200040, Peoples R China;
[5]Henan Prov Peoples Hosp, Dept Neurosurg, Zhengzhou 450003, Henan, Peoples R China;
[6]Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China;
[7]Univ New South Wales, Cure Brain Canc Fdn Biomarkers & Translat Res Grp, Lowy Canc Res Ctr, Prince Wales Clin Sch, Sydney, NSW, Australia;
[8]Harvard Med Sch, Brigham & Womens Hosp, Ctr Nanomed, Boston, MA 02115 USA;
[9]Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA
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