Calcium-doped mesoporous silica nanoparticles as a lysosomolytic nanocarrier for amine-free loading and cytosolic delivery of siRNA

Title
Calcium-doped mesoporous silica nanoparticles as a lysosomolytic nanocarrier for amine-free loading and cytosolic delivery of siRNA
Authors
김세훈최은실임동권
Issue Date
2020-01
Publisher
Journal of industrial and engineering chemistry
Citation
VOL 81-80
Abstract
For efficacious gene therapeutics, cytosolic transport of the endocytosed siRNA is crucial, not to mention a non-toxic delivery carrier composition. In this paper, we report facile achievement of amine-free loading and lysosomolytic delivery of siRNA in an unconventional way by using calcium (Ca2+)-doped mesoporous silica nanoparticles (CMSNs) as a host material along with a pore-loaded endosomal disruptor, chloroquine (CQ). It is demonstrated that CMSNs are capable of direct siRNA loading through Ca2+-incorporated larger pores, as well as efficient release of the loaded siRNA under pH control thanks to the high degradability of the Ca2+-doped silica backbone. A therapeutic performance of siRNA-loaded CMSNs is exemplified in vitro with SKOV3 human ovarian cancer cells, which underwent distinct knockdown of a target anti-apoptotic Bcl-2 gene and consequent apoptosis after incubation with those particles. When co-loaded with CQ, particles were shown to substantially promote the cytosolic delivery of the endocytosed siRNA via endo/lysosomal escape for more effective induction of cell apoptosis. The results suggest that a variety of target-genes can be applicable to the presented delivery system on demand, providing a highly versatile feature of our nanocarrier for many gene-therapeutic applications with higher efficacy.
URI
http://pubs.kist.re.kr/handle/201004/70782
ISSN
1226-086X
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KIST Publication > Article
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