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.
Original language | English |
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Pages (from-to) | 71-80 |
Number of pages | 10 |
Journal | Journal of Industrial and Engineering Chemistry |
Volume | 81 |
DOIs | |
Publication status | Published - 2020 Jan 25 |
Bibliographical note
Funding Information:This work was supported by grants from the National Research Foundation of Korea ( 2017M3A9D8029942 and 2014M3A6B2060522 ), the Korea Health Industry Development Institute ( HI15C1540 ) and the Development of Platform Technology for Innovative Medical Measurements Program from Korea Research Institute of Standards and Science ( KRISS-2018-GP2018-0018 ).
Publisher Copyright:
© 2019 The Korean Society of Industrial and Engineering Chemistry
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
Keywords
- Calcium
- Endosomal escape
- Gene silencing
- Mesoporous silica
- siRNA
ASJC Scopus subject areas
- General Chemical Engineering