Treatment of melanoma: microparticles "stuffed" with antibodies
Researchers at the Pacific Northwest National Laboratory and the University of Washington claim that packaging antitumor antibodies in porous particles of chemically modified silicon oxide increases the effectiveness of their action on a malignant skin tumor - melanoma. The results obtained by them in experiments on mice are published in the preliminary on-line version of the Journal of the American Chemical Society in the article "Local Release of Highly Loaded Antibodies from Functionalized Nanoporous Support for Cancer Immunotherapy".
Antitumor monoclonal antibodies are one of the most promising types of antitumor drugs. Such antibodies interact specifically with specific proteins on the surface of tumor cells and trigger the mechanisms of the patient's own immune system, which destroys these cells. The most well-known examples are herceptin (herceptin) and cetuximab (cetuximab), intended for the treatment of one of the types of breast cancer and rectal cancer, respectively.
The disadvantage of drugs based on monoclonal antibodies is the need for slow drip intravenous administration, which requires additional time and money, as well as the possibility of side effects due to the systemic effect of the drug.
The inclusion of antibodies in the surface of nano- or microparticles ensures their accumulation in the tumor area, which reduces the likelihood of side effects. Taking into account the previously proven biocompatibility of silicon oxide, the authors of the work opted for mesoporous particles made of this material. They developed particles measuring 6-12 micrometers containing many nanopores shaped like hexagons with a diameter of about 30 nanometers. Pores in which silicon oxide molecules are modified with the help of small chemical groups are able to hold antibodies, enzymes and other proteins inside the particles. Such packaging is "leaky", and the proteins enclosed in it gradually leak out, providing a prolonged effect of the drug. At the same time, the rate of release depends both on the drug itself and on the nature of the chemical groupings used in the modification of pores (for example, amines or residues of carboxylic or sulfonic acids).
Additional biochemical testing showed that the antibodies released by the particles retain both their structure and their antitumor properties.
To conduct experiments on mice, the researchers filled the particles with anti-CTLA4 antibodies that affect various types of cancer, including melanoma. The mice were previously divided into three groups. Particles loaded with antibodies were injected into the tumors of mice of the experimental group, and antibody preparation or empty particles were injected into the tumors of mice of the two control groups.
At the beginning of the experiment, the size of the tumors was approximately 27 cubic millimeters. Five days after the injection, the size of untreated tumors increased to 200 cubic millimeters. Tumors injected with free antibodies reached the same size only on the ninth day, which demonstrates the antitumor effect of antibodies. In mice injected with antibody-filled particles, tumors grew to 200 mm3 only after 30 days.
The repeated experiment demonstrated that the dosage form developed by the authors significantly increases the life expectancy of experimental animals. Thus, all five mice injected with empty particles died within 21 days after administration. Three of the five animals injected with antibody-filled nanoparticles were alive on day 21, and two mice of the experimental group were alive at the end of the experiment (day 34 after administration).
The authors also conducted additional experiments to assess the accumulation of antibodies in tumors. The analysis carried out two and four days after the administration of the drug revealed significantly higher concentrations of antibodies in the tumors of animals that received injections of antibody-filled particles, compared with the tumors of animals that were injected with free antibodies.
Currently, researchers are testing the effectiveness of other antibody-tumor pairs on mice. In the future, they plan to study the mechanisms underlying the increase in the effectiveness of antibodies packaged in this way, as well as conduct experiments using larger animal models with the prospect of applying the results obtained in clinical trials.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the Pacific Northwest National Laboratory: Silica cages help anti-cancer antibodies kill tumors in mice.
03.06.2010