Chemotherapy of glioblastoma by targeted liposomal platinum compounds with focused ultrasound

Abstract

Giloblastoma multiforme (GBM) is the most aggressive brain neoplasm, and patients have a poor prognosis after radiation and chemotherapy. The chemotherapy protocols still marginally improve the anti-tumor effect of patients with glioblastoma because the therapeutic dosage of many drugs is impeded by the blood-brain barrier (BBB). The use of liposomal drugs to GBM treatment might benefit from a more crossing of the BBB due to the lipid nature achieving higher doses of drug at the tumor sites. Human GBM-bearing mice were injected intravenously with cisplatin encapsulated in atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes or unconjugated liposome. Moreover, the administration of AP-1 liposomal cisplatin (lipoplatin) followed by focused ultrasound (FUS)-induced BBB disruption. Tumor progression was monitored by biophotonic imaging. The preliminary data demonstrated that the GBM chemotherapy with AP-1 lipoplatin followed by pulsed FUS showed a modest improvement of tumor growth in the brain compared to the group treated with lipoplatin alone. Further investigations are needed to use this new targeted lipoplatin in treatment of malignancies.