Chemotherapy treatments have strong side effects such as hair and weight loss, fatigue, nausea and vomiting. Researchers have found that a new agent that accumulates in tumor tissue and is activated by ultrasound waves does not cause these side effects.
Platinum complexes are among the most widely used anticancer drugs. They are successful, but with many serious side effects. An international research team led by Dr. Johannes Karges of Ruhr University Bochum, Germany, has now found an alternative, the university said in a statement press release.
The cell-damaging effect of the new drug only manifests itself where it is actually desired. “While previous studies relied on light activation that can penetrate only a few millimeters deep into the tissue, we have now developed a treatment method with ultrasonic activation that penetrates a few centimeters deep into the body,” says Karges. This could enable treatment with few side effects, even for large and deep-seated tumours.
Harmless in healthy tissue
The platinum(II) complexes cisplatin, oxaliplatin and carboplatin are among the most commonly used anticancer drugs. Their clinical success is offset by serious side effects, such as nausea, vomiting, kidney damage and bone marrow suppression. To overcome these limitations, major research efforts have been invested in the development of so-called platinum(IV) complex prodrugs in recent decades. “These drugs are stable and inactive, so they are completely harmless,” explains Karges. “In healthy tissue, they are supposed to stay that way. In cancer tissue, however, they must be rapidly converted into the therapeutically active platinum(II) complexes.”
Energy is required for the reduction of the metal complex. Previous studies reported activation with ultraviolet, blue or red light. “The problem is that light can only penetrate less than a centimeter deep into the body and thus does not reach many tumors,” says Karges. To overcome this limitation, his team developed platinum(IV) complex for the first time prodrugs combined with sonosensitizers that can be selectively activated with ultrasonic irradiation.
Nanoparticles accumulate in the tumor
To develop a therapeutically effective complex, the researchers encapsulated the platinum(IV) complex prodrugs and the sonosensitizers together in hemoglobin into nanoparticles. Karges: “We were able to determine that the nanoparticles selectively accumulate in a mouse intestinal tumor after injection into the bloodstream, which supports targeted treatment. After ultrasound irradiation, the platinum(IV) prodrug was activated at the tumor site, releasing cisplatin toxic to the cells and nearly eradicating the tumor.”
Advantages of Ultrasound
These results could pave the way for the development of new techniques and agents for the treatment of very large or deep-seated tumours. Ultrasound can penetrate more than an order of magnitude deeper into tissue than near-infrared light. In addition, ultrasound treatments are generally considered less invasive and easy to use. Another advantage is that hospitals usually already have the necessary equipment. “Our work is still fundamental research,” emphasizes Karges. “Whether and when treatments based on this can be offered in clinical practice cannot yet be foreseen.”