The siRNAsome: A Cation-Free and Versatile Nanostructure for siRNA and Drug Co-delivery.
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.
['Zheng|Meng|M|0000-0003-2932-1062', 'Jiang|Tong|T|', 'Yang|Wen|W|', 'Zou|Yan|Y|', 'Wu|Haigang|H|', 'Liu|Xiuhua|X|', 'Zhu|Fengping|F|', 'Qian|Rongjun|R|', 'Ling|Daishun|D|', 'McDonald|Kerrie|K|', 'Shi|Jinjun|J|', 'Shi|Bingyang|B|0000-0002-1043-3163']
D000903:Antibiotics, Antineoplastic D001943:Breast Neoplasms D049109:Cell Proliferation D002470:Cell Survival D004317:Doxorubicin D016503:Drug Delivery Systems D018432:Drug Resistance, Multiple D004354:Drug Screening Assays, Antitumor D006801:Humans D057927:Hydrophobic and Hydrophilic Interactions D061986:MCF-7 Cells D049329:Nanostructures D034741:RNA, Small Interfering
nanostructures siRNA co-delivery vesicles synergistic therapy