Inorganic nanoparticles for cancer therapy
File(s)
Author(s)
McFarlane, Taneisha
Type
Thesis
Abstract
Breast cancer is among the most prevalent cancers globally, with 2.26 million cases diagnosed annually. Current treatments, particularly for aggressive breast cancers lacking hormone receptors, are limited by significant side effects, highlight the urgent need for more innovative therapies.
Nanoparticles (NPs), ranging from 1nm to 100nm, offer potential as imaging agents and drug carriers. However, conventional nanomedicines, often based on chemotherapeutics, remain highly toxic and primarily target primary tumours while neglecting metastatic risks, such as those to bone tissue.
This research focuses on developing and testing germania, germania-silica and SiO2-ZnO-SrO inorganic nanoparticles, for selective breast cancer targeting, sparing normal cells and bone health enhancement, without chemotherapeutic drugs. SiZnSr nanoparticles with a Si:Zn:Sr ratio of 1:2.6:5 were synthesized using a modified Stöber method, producing monodisperse particles (80 ± 30nm) containing 17 mol% ZnO and 13 mol% SrO. These ions, released more rapidly in acidic environments, were crucial for achieving selective cytotoxicity, stability, and monodispersity.
Cellular studies, with the use of transmission electron microscopy (TEM) demonstrated SiZnSr 1:2.6:5 nanoparticles selective internalisation in breast cancer (MCF-7, MDA-MB231), osteosarcoma (Saos-2), and primary breast cancer explants, while sparing normal breast cells (MCF-10A), osteoblasts (NHoBs), and macrophage-like cells (RAW 264.7). Cytotoxicity studies revealed effective cancer cell death in MCF-7 and MDA-MB231 breast cancer cell lines, explant breast cancer cells and Saos-2 osteosarcoma cell lines, while preserving normal cell viability in while preserving MCF-10A, normal explant breast cells and primary human osteoblast cells. NHoBs exhibited enhanced bone mineralization over 21 days, with elevated levels of bone morphogenetic proteins BMP2 and BMP4 and other bone markers.
These findings indicate SiZnSr 1:2.6:5 nanoparticles’ potential as a dual-function therapy: selectively targeting breast cancer cells and promoting bone health, addressing critical gaps in current treatment approaches.
Nanoparticles (NPs), ranging from 1nm to 100nm, offer potential as imaging agents and drug carriers. However, conventional nanomedicines, often based on chemotherapeutics, remain highly toxic and primarily target primary tumours while neglecting metastatic risks, such as those to bone tissue.
This research focuses on developing and testing germania, germania-silica and SiO2-ZnO-SrO inorganic nanoparticles, for selective breast cancer targeting, sparing normal cells and bone health enhancement, without chemotherapeutic drugs. SiZnSr nanoparticles with a Si:Zn:Sr ratio of 1:2.6:5 were synthesized using a modified Stöber method, producing monodisperse particles (80 ± 30nm) containing 17 mol% ZnO and 13 mol% SrO. These ions, released more rapidly in acidic environments, were crucial for achieving selective cytotoxicity, stability, and monodispersity.
Cellular studies, with the use of transmission electron microscopy (TEM) demonstrated SiZnSr 1:2.6:5 nanoparticles selective internalisation in breast cancer (MCF-7, MDA-MB231), osteosarcoma (Saos-2), and primary breast cancer explants, while sparing normal breast cells (MCF-10A), osteoblasts (NHoBs), and macrophage-like cells (RAW 264.7). Cytotoxicity studies revealed effective cancer cell death in MCF-7 and MDA-MB231 breast cancer cell lines, explant breast cancer cells and Saos-2 osteosarcoma cell lines, while preserving normal cell viability in while preserving MCF-10A, normal explant breast cells and primary human osteoblast cells. NHoBs exhibited enhanced bone mineralization over 21 days, with elevated levels of bone morphogenetic proteins BMP2 and BMP4 and other bone markers.
These findings indicate SiZnSr 1:2.6:5 nanoparticles’ potential as a dual-function therapy: selectively targeting breast cancer cells and promoting bone health, addressing critical gaps in current treatment approaches.
Version
Open Access
Date Issued
2024-02-01
Date Awarded
2024-12-01
Copyright Statement
Attribution-Non Commercial-No Derivatives 4.0 International Licence (CC BY-NC-ND)
Advisor
Jones, Julian
Porter, Alexandra
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)