August 7, 2006
Nanoparticle-Drug Combo Stops Tumor-Associated Angiogenesis
By encapsulating a drug already approved to treat a side effect of cancer inside liposomal nanoparticles, researchers at the University of Zürich have developed an agent that stops tumor-associated angiogenesis and reduces tumor growth by as much as 92 percent. This new potential anticancer agent works by depleting the number of a specific type of immune system cell thought to be associated with tumor growth and metastasis. This work appears in the British Journal of Cancer.
Reto Schwendener, Ph.D., and colleagues developed a liposomal formulation of the drug clodronate to target tumor-associated macrophages, immune system cells that actually promote tumor growth and angiogenesis. Research had already demonstrated that clodronate, a drug now used to inhibit bone shrinkage that can occur in cancer patients, can inhibit angiogenesis, and tests with cultured tumor-associated macrophages showed that liposomal clodronate was toxic to these particular cells.
Using a mouse model of human rhabdomyosarcoma, a malignant tumor of muscles, the investigators found that liposomal clodronate drastically reduced the density of blood vessels in tumors, depleted tumor-associated macrophages, and markedly reduced tumor growth. Antitumor activity was even more pronounced when this new agent was administered with antibodies that bind to vascular endothelial growth factor (VEGF), a molecule that triggers new blood growth. This study did find, however, that treatment was not able to fully suppress tumor growth and noted that this therapy would therefore be useful only in combination with other forms of chemotherapy, as is true with other anti-angiogenesis agents.
This work is detailed in a paper titled, “Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach.” Investigators from the Paul Scherrer Institute in Villigen-PSI, Switzerland, also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.