The group, led by Prof Julian R Jones, had previous successes in using these particles to deliver ions inside cells, so for this study, they turned their attention to zinc. The material has been shown to have potential as an anti-cancer treatment, but its rapid degradation in the bloodstream means that it can fail to reach its target. By trapping Zn2+ ions within a chemically-tuned silica matrix, the release of zinc could be delayed, allowing the ions to reach the cells, unaltered. These “monodispersed zinc-containing silica-based mesoporous bioactive glass nanoparticles” (MSNPs-Zn) were fabricated via a multi-step process; their mean diameter was found to be 54.6 ±8.9 nm, with each pore measuring ~4 nm across.
To test the efficacy of the MSNPs-Zn as a therapeutic, the researchers cultured a series of different cell lines; from human breast cancer cells that respond to hormone treatment, to highly-aggressive triple-negative cancer cells that don’t. Bone marrow-derived macrophages were also obtained from mice, and healthy human epithelial cells acted as the control.
The result of these in vitro tests were surprising, even to Jones – the MSNPs-Zn were internalized by both types of breast cancer cells, and were toxic to them. The healthy cells and macrophages were entirely unaffected. Jones said, “What we were really surprised by was how well it worked in terms of the width of the working dose range.” Their results suggest that at doses between 75 and 125 µg/mL, MSNPs-Zn could act as a selective therapeutic. Most interestingly, he continued “it killed the more aggressive type of cancer cells more rapidly than the other cancer cells.”
The team also investigated the release of zinc in a rage of environments, and found that it was highly dependent on pH, which could offer a degree of control. As they wrote, this means its release “will be faster at a low pH tumour environment…but slow in blood plasma….. It will reduce the persistence of particles that reach systemic sites in the body.”
When asked about the possible implication of his work, Jones said, “In a way, the results seem a bit too good to be true in terms of actually treating patients. In practice, the particles may not reach all tumour cells, but perhaps they could at least reduce tumour growth and slow production of metastases, without causing side effects.” But, he cautioned, there is still a long way to go before these particles can reach a clinical trial. “The delivery method needs to be identified and proven, and the particles themselves must have regulatory approval, which is an onerous task. We’ll also need to establish a good manufacturing practice to produce the particles, and carry out specific animal studies. This technology is at a very early stage, and if we want to continue it, we’ll need investment.”
—
References
1] https://www.bcrf.org/breast-cancer-statistics-and-resources
2] https://esmoopen.bmj.com/content/2/4/e000208
This story was written for Materials Today: https://www.materialstoday.com/biomaterials/news/silica-nanoparticles-for-cancer-therapy/
Research paper ($): S. Chena, S.L. Greasley, Z.Y. Ong, P. Naruphontjirakul, S.J. Page, J.V. Hanna, A.N. Redpath, O. Tsigkou, S. Rankin, M.P. Ryan, A.E. Porter, J.R. Jones. “Biodegradable zinc-containing mesoporous silica nanoparticles for cancer therapy”, Materials Today Advances, article in press. DOI: 10.1016/j.mtadv.2020.100066
