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Frizzled-7-targeted delivery of zinc oxide nanoparticles to drug-resistant breast cancer cells.
Ruenraroengsak, Pakatip; Kiryushko, Darya; Theodorou, Ioannis G; Klosowski, Michal M; Taylor, Erik R; Niriella, Thisa; Palmieri, Carlo; Yagüe, Ernesto; Ryan, Mary P; Coombes, R Charles; Xie, Fang; Porter, Alexandra E.
Afiliación
  • Ruenraroengsak P; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk and Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok, 10400, Thailand.
  • Kiryushko D; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
  • Theodorou IG; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
  • Klosowski MM; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
  • Taylor ER; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
  • Niriella T; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
  • Palmieri C; Institute of Translational Medicine, University of Liverpool, L693BX, Liverpool, UK.
  • Yagüe E; Division of Cancer, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
  • Ryan MP; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
  • Coombes RC; Division of Cancer, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
  • Xie F; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
  • Porter AE; Department of Materials and London Centre for Nanotechnology, Imperial College London, Exhibition Road, London SW7 2AZ, UK. a.porter@imperial.ac.uk.
Nanoscale ; 11(27): 12858-12870, 2019 Jul 11.
Article en En | MEDLINE | ID: mdl-31157349
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Óxido de Zinc / Neoplasias de la Mama / Portadores de Fármacos / Receptores Frizzled / Nanopartículas / Antineoplásicos Inmunológicos Límite: Female / Humans Idioma: En Revista: Nanoscale Año: 2019 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Óxido de Zinc / Neoplasias de la Mama / Portadores de Fármacos / Receptores Frizzled / Nanopartículas / Antineoplásicos Inmunológicos Límite: Female / Humans Idioma: En Revista: Nanoscale Año: 2019 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido