Frizzled-7-targeted delivery of zinc oxide nanoparticles to drug-resistant breast cancer cells
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-07-21
Date Acceptance
2019-05-26
Citation
Nanoscale, 2019, 11 (27), pp.12858-12870
ISSN
2040-3364
Publisher
Royal Society of Chemistry
Start Page
12858
End Page
12870
Journal / Book Title
Nanoscale
Volume
11
Issue
27
Copyright Statement
© 2019 The Royal Society of Chemistry.
Sponsor
Royal Academy Of Engineering
Commission of the European Communities
Breast Cancer Care & Breast Cancer Now
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31157349
Grant Number
MMRE_P56611
PIEF-GA-2013-627049
2014NovPhD326
Subjects
Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Physics, Applied
Chemistry
Science & Technology - Other Topics
Materials Science
Physics
COLLATERAL SENSITIVITY
P53
APOPTOSIS
GROWTH
10 Technology
02 Physical Sciences
03 Chemical Sciences
Nanoscience & Nanotechnology
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2019-05-28