Co-delivery of STAT3 siRNA and methotrexate in breast cancer cells

Zahra Shakeran, Jaleh Varshosaz*, Mehrnaz Keyhanfar*, Hossein Mohammad-Beigi, Karim Rahimi, Duncan S. Sutherland*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Co-delivery of anticancer drugs and biologics can provide synergetic effects and outperform single delivery therapies. Here, a nanoparticle (NP) system for co-delivery of methotrexate (MTX) and STAT3 siRNA has been developed and tested in vitro. Mesoporous silica nanoparticles (MSNs) were functionalized with chitosan (ch) by covalent grafting mediated by aminopropyl triethoxysilane (APTES) via glutaraldehyde as the linker. Co-delivery of MTX and STAT3 siRNA to MCF7 cells was demonstrated in cells by flow cytometric analysis and confocal laser scanning fluorescence microscopy for use in breast cancer treatment. MTX either competitively inhibits the dihydrofolate reductase (DHFR) receptor or suppresses the STAT3 metabolic pathway. STAT3 protein plays an essential role in cell division, proliferation and survival. Reduction of the protein by both MTX and STAT3 siRNA, achieved by chMSNs, significantly decreased the viability of breast cancer cells compared to single treatments alone. Cellular uptake of modified NPs was increased over time when additional free MTX was added implicating the DHFR receptor in uptake. In addition, protein corona compositions coated the NPs outer surface, were different between the NPs with and without drug potentially modulating cellular uptake. This study is the first report on co-delivery of MTX and STAT3 siRNA by chitosan modified MSNs.
Original languageEnglish
JournalArtificial Cells, Nanomedicine and Biotechnology
Volume50
Issue number1
Pages (from-to)29-39
Number of pages11
ISSN2169-1401
DOIs
Publication statusPublished - 2022

Keywords

  • Mesoporous silica nanoparticles
  • Methotexate
  • STAT3
  • sIRNA
  • Co-delivery
  • Breast cancer cells
  • Protein corona

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