Researchers from University of Washington and Pacific Northwest National Laboratory have developed silica cages that can help deliver anti-cancer antibodies to tumors. Scientists have also shown that their technique can prolong life span of mice with cancer. The silica structure permits the slow and regular release of antibodies, which may one day help oncologists deliver treatment in a controlled fashion.
Packaging antibodies into particles would concentrate them at the tumor and possibly reduce side effects. Other research has shown silicon to be well tolerated by cells, animals and people. So, in collaboration with tumor biologist Karl Erik Hellstrom’s group at UW, the scientists explored particles made from material called mesoporous silica against cancer in mice.
In previous work, the team created particles that contain nano-sized hexagonal pores that hold antibodies, enzymes or other proteins. In addition, adorning the silica pores with small chemical groups helps trap proteins inside. But not permanently — these proteins slowly leak out like a time-release capsule.
The researchers wanted to test whether anti-cancer antibodies packaged in modified mesoporous silica would be more effective against tumors than free-flowing antibodies.
To do so, they first chemically modified mesoporous silica particles of about six to 12 micrometers (about 1/10 the diameter of human hair). These particles contained pores of about 30 nanometers in diameter. They found that the extent and choice of chemical modification — amine, carboxylic acid or sulfonic acid groups — determined how fast the antibodies leaked out, a property that can be exploited to fine tune particles to different drugs.
Additional biochemical tests showed that the antibodies released from the silica cages appeared to be structurally sound and worked properly.
They then tested the particles in mouse tumors at UW, filling them with an antibody called anti-CTLA4 that fights many cancers, including melanoma, a skin cancer. The team injected these packaged antibodies into mouse tumors. The team also injected antibodies alone or empty particles in other mouse tumors.
The packaged antibodies slowed the growth of tumors the best. Treatment started when tumors were about 27 cubic millimeters. Untreated tumors grew to 200 cubic millimeters about 5 days post-treatment. Tumors treated with antibodies alone reached 200 cubic millimeters on day 9, showing that antibodies do slow tumor growth. But tumors treated with packaged antibodies didn’t reach 200 cubic millimeters until day 30, a significant improvement over antibodies alone.
The team repeated the experiment and found the treatment also prolonged the lives of diseased mice. Of five mice that had been treated with particles alone, all died within 21 days after treatment. But of five mice treated with the packaged antibodies, three were still alive at 21 days, and two at 34 days, when the experiment ended.
The team also measured how much antibody remained in the tumors. Two and four days after injection, the researchers found significantly more antibody in tumors when the antibodies had been encased in the silica particles than when the antibodies had been injected alone.
Press release: Silica cages help anti-cancer antibodies kill tumors in mice…
Abstract in Journal of The American Chemical Society: Local Release of Highly Loaded Antibodies from Functionalized Nanoporous Support for Cancer Immunotherapy