Accomplishing significantly enhanced overall survivability (OS) remains a formidable challenge in combating glioblastoma. The presence of the blood-brain barrier acts as the major biological barrier in delivering drugs to the brain. Herein, liposomal formulations of two novel nicotinylated amphiphiles are reported for targeting potent anticancer drugs to orthotopic mouse glioblastoma. It is shown that intravenous administration of the potent signal transducer and activator of transcription 3 (STAT3) inhibitor (WP-1066)-loaded liposomes of nicotinylated amphiphiles in combination with in vivo dendritic cell (DC)-targeted subcutaneous genetic immunization (using tyrosinase-related protein-2 encoded DNA vaccine) markedly enhances the OS of orthotopic glioblastoma-bearing mice (by >500% compared to the OS for the control group). Notably, the overall survival benefits in orthotopic-brain-tumor-bearing mice treated with only targeted chemotherapy or with only in vivo DC-targeted genetic immunization are found to be significantly less. The presently described simple approach avoids the need of isolation of any autologous immune cells. In summary, the preclinical findings described herein open the door for combating glioblastoma in humans through harnessing synergistic effects of targeted chemotherapy and in vivo DC-targeted genetic immunization.
Keywords: BBB-crossing liposome; combination therapy; glioblastoma; in vivo DC-targeted DNA vaccination; nicotinylated cationic lipid.
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.