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

Eunshil Choi, Dong Kwon Lim, Sehoon Kim

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)71-80
    Number of pages10
    JournalJournal of Industrial and Engineering Chemistry
    Volume81
    DOIs
    Publication statusPublished - 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

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