Credit: Heinrich Volschenk

One challenge in cancer treatment is to balance toxicity with specificity: potential therapies must be toxic enough to damage rapidly dividing cancer cells yet specific enough to not harm other tissues. Cytolytic peptides are small proteins that are drawn to cell membranes and destroy them by creating structural defects that cause the cells to break apart. The peptides have antibiotic, anti-inflammatory and anticancer properties, and their mechanism of action is such that cells cannot easily develop resistance to them. These characteristics make them potentially valuable in cancer treatment if they can be effectively targeted to tumors. Melittin is a particularly toxic but nonspecific cytolytic peptide that naturally occurs in the venom of the honeybee (Apis mellifera). In a new study, researchers packaged melittin in nano-spheres to deliver it directly to tumor cells without harming other tissues.

Paul Schlesinger and colleagues at Washington University School of Medicine (St. Louis, MO) had previously developed the nano-spheres, which contain a core composed of perfluorocarbon, an inert component of artificial blood. They are large enough to carry active compounds but small enough to circulate through the bloodstream and attach to cell membranes. The nano-spheres protect melittin from enzymatic degradation and prevent it from harming normal cells. The spheres tend to collect in solid tumors because tumors have greater permeability and retention than do normal cells, and the spheres can also be loaded with molecules that direct them to tumors.

The new study used mice carrying human breast cancer tumors or melanomas. After injecting the mice with nano-spheres carrying melittin, Schlesinger's group noted that tumor growth slowed and some tumors even began to shrink (J. Clin. Invest. published online 10 August 2009; doi:10.1172/JCI38842). Growth of breast cancer tumors slowed by ∼25%, and melanoma tumors shrank by ∼88%.

Having determined that the nano-spheres could reliably deliver melittin to established tumors, the researchers wondered if they would be effective against early-stage neoplasms or even precancerous cells. For these experiments, Schlesinger and colleagues used mice with a precancerous stage of squamous carcinoma. After loading nano-spheres with both melittin and a tumor-targeting molecule and injecting them into mice, the researchers noted an 80% reduction in the proliferation of precancerous cells.

None of the mice in the study showed any signs of toxicity; they had normal blood cell counts and no indications of organ damage. The researchers concluded that their nano-spheres are an effective means of delivering cytolytic peptides that could be developed for cancer treatment.