Combating Established Mouse Glioblastoma through Nicotinylated‐Liposomes‐Mediated Targeted Chemotherapy in Combination with Dendritic‐Cell‐Based Genetic Immunization. Issue 1 (11th January 2017)

• Record Type: Journal Article
• Authors: Saha, Soumen; Venu, Yakati; Bhattacharya, Dwaipayan; Kompella, Shobha Deepthi; Madhusudana, Kuncha; Chakravarty, Sumana; Ramakrishna, Sistla; Chaudhuri, Arabinda
• Is Part Of: Advanced biosystems. Volume 1 :Issue 1/2 (2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-01-11
• Subjects: BBB‐crossing liposome -- combination therapy -- glioblastoma -- in vivo DC‐targeted DNA vaccination -- nicotinylated cationic lipid; Biological systems -- Periodicals; Biotechnology -- Periodicals; Bioengineering -- Periodicals; Biomedical engineering -- Periodicals; Biological Science Disciplines; Periodicals; Periodicals; 660.6
• DOI: 10.1002/adbi.201600009
• Languages: English
• ISSNs: 2366-7478

Abstract

Abstract : 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. Abstract : The present study reports on combating established orthotopic mouse glioblastoma by targeted chemotherapy in combination with in vivo dendritic cell (DC)‐targeted genetic immunization. The combination approach elicits enhanced overall survivability (more than 500% compared to untreated mice) of orthotopic glioblastoma bearing mice without the need of isolation and ex vivo engineering of recipient's autologous immune cells.