Injectable, self-assembling structures could fight cancer

A non-surgical injection of "programmable biomaterial" - capable of spontaneously assembling into a 3D structure when inside a living organism - may be able to fight and prevent cancer and other serious diseases, according to a joint project from Harvard researchers at the Wyss Institute for Biologically Inspired Engineering and School of Engineering and Applied Sciences, both in Cambridge, MA.

Mesoporous silica rods spontaneously assemble to form a porous 3D scaffold. The 3D scaffold has many nooks and crannies and is large enough to house tens of millions of recruited immune cells.
Image credit: Wyss Institute at Harvard University

The Harvard teams are researching the use of biodegradable rods, known as mesoporous silica rods (MSRs), to deliver drugs via an injection. When the drugs reach the vaccination site, they assemble spontaneously into a 3D scaffold, in a manner that the researchers compare to pouring a box of matchsticks into a pile on a table.

Tens of millions of dendritic cells swarm to the structure and take up residence within the nooks and crannies of the MSR scaffold. These "surveillance" cells monitor the body - when a harmful presence is detected, they trigger an immune response.

The researchers at the Wyss Institut, and at Sungkyunkwan University can create 3D structures using minimally-invasive delivery to enrich and activate a host's immune cells to target and attack harmful cells in vivo 

Study is the first to use mesoporous silica scaffolds to recruit immune cells

"Nano-sized mesoporous silica particles have already been established as useful for manipulating individual cells from the inside, but this is the first time that larger particles, in the micron-sized range, are used to create a 3D in vivo scaffold that can recruit and attract tens of millions of immune cells."

When the MSRs are built in the lab, the rods are constructed with many small holes - "nanopores" - that can be loaded with drugs as required to fight infection. When the dendritic cells are recruited from the body to the scaffold, the drugs contained in the nanopores are released, which triggers an immune response in the dendritic cells.

Once activated into an immune response, the dendritic cells leave the scaffold, traveling to the lymph nodes, where they direct the immune system to attack specific cells, such as cancer cells. Meanwhile, the MSR structure biodegrades and dissolves naturally.

A microscope image shows many of the immune system's dendritic cells that were collected from a 3D scaffold 3 days after in vivo injection.
Image credit: Wyss Institute at Harvard University

Although right now the researchers are focusing on developing a cancer vaccine, in the future we could be able to manipulate which type of dendritic cells or other types of immune cells are recruited to the 3D scaffold by using different kinds of cytokines released from the MSRs.

By tuning the surface properties and pore size of the MSRs, and therefore controlling the introduction and release of various proteins and drugs, we can manipulate the immune system to treat multiple diseases.

3D vaccine is 'highly effective' in mouse trials

This novel MSR vaccine has been tested in mice and found to be "highly effective," according to the authors, who publish their findings in the journal Nature Biotechnology.

The researchers believe that the vaccines could be made widely available and deployed quickly to deal with epidemics as they can be easily and rapidly manufactured.

As well as fighting infections and specific kinds of cells, the 3D vaccine may also be an effective preventative therapy, as the same immune response-triggering mechanism could be used to strengthen immune resistance in advance of an infection.

"Injectable immunotherapies that use programmable biomaterials as a powerful vehicle to deliver targeted treatment and preventative care could help fight a whole range of deadly infections, including common worldwide killers like HIV and Ebola, as well as cancer.

These injectable 3D vaccines offer a minimally invasive and scalable way to deliver therapies that work by mimicking the body's own powerful immune response in diseases that have previously been able to skirt immune detection."

References:

1. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy, David J. Mooney, et al., Nature Biotechnology, doi:10.1038/nbt.3071, published online 8 December 2014, abstract.
2. Additional source: Wyss Institute news release, accessed 9 December 2014.