TY - JOUR
T1 - The siRNAsome
T2 - a cation free and versatile nanostructure for siRNA and drug codelivery
AU - Zheng, Meng
AU - Jiang, Tong
AU - Yang, Wen
AU - Zou, Yan
AU - Wu, Haigang
AU - Liu, Xiuhua
AU - McDonald, Kerrie
AU - Ling, Daishun
AU - Shi, Jinjun
AU - Zhu, Fengping
AU - Qian, Rongjun
AU - Shi, Bingyang
N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - co-delivery
KW - nanostructures
KW - siRNA
KW - synergistic therapy
KW - vesicles
UR - http://www.scopus.com/inward/record.url?scp=85062350670&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/nhmrc/1111611
U2 - 10.1002/anie.201814289
DO - 10.1002/anie.201814289
M3 - Article
C2 - 30737876
AN - SCOPUS:85062350670
SN - 1433-7851
VL - 58
SP - 4938
EP - 4942
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 15
ER -