Publication: Frizzled-7-targeted delivery of zinc oxide nanoparticles to drug-resistant breast cancer cells
Issued Date
2019-07-21
Resource Type
ISSN
20403372
20403364
20403364
Other identifier(s)
2-s2.0-85069513073
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Mahidol University
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SCOPUS
Bibliographic Citation
Nanoscale. Vol.11, No.27 (2019), 12858-12870
Suggested Citation
Pakatip Ruenraroengsak, Darya Kiryushko, Ioannis G. Theodorou, Michał M. Klosowski, Erik R. Taylor, Thisa Niriella, Carlo Palmieri, Ernesto Yagüe, Mary P. Ryan, R. Charles Coombes, Fang Xie, Alexandra E. Porter Frizzled-7-targeted delivery of zinc oxide nanoparticles to drug-resistant breast cancer cells. Nanoscale. Vol.11, No.27 (2019), 12858-12870. doi:10.1039/c9nr01277j Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51173
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Title
Frizzled-7-targeted delivery of zinc oxide nanoparticles to drug-resistant breast cancer cells
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Abstract
© The Royal Society of Chemistry. There is a need for novel strategies to treat aggressive breast cancer subtypes and overcome drug resistance. ZnO nanoparticles (NPs) have potential in cancer therapy due to their ability to potently and selectively induce cancer cell apoptosis. Here, we tested the in vitro chemotherapeutic efficacy of ZnONPs loaded via a mesoporous silica nanolayer (MSN) towards drug-sensitive breast cancer cells (MCF-7: estrogen receptor-positive, CAL51: triple-negative) and their drug-resistant counterparts (MCF-7TX, CALDOX). ZnO-MSNs were coated on to gold nanostars (AuNSs) for future imaging capabilities in the NIR-II range. Electron and confocal microscopy showed that MSN-ZnO-AuNSs accumulated close to the plasma membrane and were internalized by cells. High-resolution electron microscopy showed that MSN coating degraded outside the cells, releasing ZnONPs that interacted with cell membranes. MSN-ZnO-AuNSs efficiently reduced the viability of all cell lines, and CAL51/CALDOX cells were more susceptible than MCF7/MCF-7-TX cells. MSN-ZnO-AuNSs were then conjugated with the antibody to Frizzled-7 (FZD-7), the receptor upregulated by several breast cancer cells. We used the disulphide (S-S) linker that could be cleaved with a high concentration of glutathione normally observed within cancer cells, releasing Zn2+ into the cytoplasm. FZD-7 targeting resulted in approximately three-fold amplified toxicity of MSN-ZnO-AuNSs towards the MCF-7TX drug-resistant cell line with the highest FZD-7 expression. This study shows that ZnO-MSs are promising tools to treat triple-negative and drug-resistant breast cancers and highlights the potential clinical utility of FZD-7 for delivery of nanomedicines and imaging probes specifically to these cancer types.