Tumor-homing
peptides are attractive tools for
tumor imaging and targeted
therapy due to their ability to specifically bind and enter
tumor cells and masses.
Bombesin and its analogues show promise for the targeted delivery of radioactive and chemotherapeutic agents to a wide variety of solid
tumors. Here, we describe the
bombesin-targeted delivery of toxic
peptides to solid
tumor cells and
leukemia cells. We found that
bombesin specifically bound to solid
tumor cells and
leukemia cells with similar affinity. Conjugation to
bombesin significantly (5-15 times) enhanced the cytotoxicity of three mitochondria-disrupting
peptides (KLA, B27, and B28) in solid
tumor cells and
leukemia cells through improvement of their binding affinity. The
bombesin-directed
peptides (KB, BB27, and BB28) contained the same
bombesin leader sequence but had different mitochondria-disrupting
peptides, which selectively induced caspase-dependent apoptosis in solid
tumor cells and
leukemia cell lines. The IC50 values of these
peptides (BB27, 3-5 micromol/L; BB28, 4-6 micromol/L) for solid
tumor cells and
leukemia cells are approximately 5-10 times lower than the IC50 values for normal cells. BB27 and BB28 also displayed cytotoxicity in primary
leukemia cells from patients (n = 4) with
acute myeloid leukemia. Intratumoral (10 mg/kg) and intraperitoneal (20 mg/kg) injection of BB27 and BB28 exerted substantial inhibition on K562
tumor xenograft growth without obvious systematic toxicity. Our results suggest that the
bombesin-directed mitochondria-disrupting
peptides BB27 and BB28 might be used as therapeutic agents not only for solid
tumors but also for hematologic
tumors.