Bioengineers, physicians and scientists working together at the Dana-Farber Cancer Institute have created, using molecular biology and biochemical engineering, a nanoparticle that simultaneously attacks bone cancer and strengthens bone damaged by cancer.
The nanoparticle reduces the tumor volume, increases bone, and most importantly, significantly extends the survival time of a model animal with multiple myeloma, a type of bone cancer. The nanoparticle was engineered to play the dual role of targeting and killing cancerous cells in bone, as well as regenerating material lost due to the deterioration caused by the cancer’s influence on the bone environment. Because cancer drugs generally flood the body even hitting tissues that are healthy (though ostensibly with a weaker effect than against diseased tissue), they have strong, negative side effects. Proper targeting the right tissues will alleviate the severity of some of these toxic side effects.
The nanoparticle was tested on a mouse with multiple myeloma, a cancer of the bone in which plasma cells proliferate wildly. Plasma cells are chemical factories, producing antibodies that assist in immune response, but also releasing chemical messages to nearby cells. In multiple myeloma, a genetic defect causes plasma cells to proliferate and accumulate. Moreover, the plasma cells produce excessive amounts of antibody protein that poisons the organism, and sends incorrect chemical signals that result in bone tissue death and degradation.
The scientists optimized the type of material used to make the nanoparticles so as to maximize circulation in blood and targeting to bone. The targeting was accomplished by coating the nanoparticle with alendronate (sold as Fosamax), a well-known medical molecule that binds to the bone matrix. In this way the nanoparticle is targeted to the bone tissue. The nanoparticle was then loaded with a special anti-cancer drug bortezomib (sold as Velcade) which shuts down the waste disposal system of the cancer cells.
Cancer cells are particularly sensitive as they produce many byproducts that need to go through the waste system. When the waste system is shut down, cancer cells are particularly vulnerable and become clogged with excess material. The drug is slowly released from the interior of the nanoparticle. Because the targeting system should bring it quickly to the bone, most of the drug will be released at the correct location.