Original source: Materials Today
Modern breast cancer treatment typically involves some combination of surgery, chemotherapy, hormone treatment and radiotherapy. Though gruelling, it works, and has vastly improved the prognosis for the > 1 million women who get diagnosed with the disease each year. The options for triple-negative breast cancers are much more limited. A particularly aggressive form of the disease, they are so named because they lack the three most common receptors that cancer drugs target. Chemotherapy has been shown to be an effective treatment, but its low selectivity means that it comes with multiple undesirable side-effects. And given that triple-negative breast cancers represent ~30% of all breast cancer-associated deaths, there is an urgent need for more targeted therapies.
Writing in Materials Today Advances [DOI: 10.1016/j.mtadv.2020.100066], researchers from Imperial College London have proposed a nanomaterial solution – zinc-loaded, porous silica nanoparticles that can act as a biodegradable delivery platform for cancer therapies.
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 dimeter 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.”
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