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Updated: Dec 15, 2025
Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model
Published on: June 4, 2017
Combating Established Mouse Glioblastoma through Nicotinylated-Liposomes-Mediated Targeted Chemotherapy in
Soumen Saha1,2, Yakati Venu1,2, Dwaipayan Bhattacharya3
1Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, 500007, Telangana, India.
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.
Insights
This study combined targeted chemotherapy with a novel DNA vaccine to significantly improve survival in glioblastoma mouse models. This approach offers a promising new strategy for treating brain tumors.
Area of Science:
- Oncology
- Immunology
- Nanotechnology
Background:
- Glioblastoma (GBM) poses a significant challenge due to poor overall survival (OS) and the blood-brain barrier (BBB) limiting drug delivery.
- Effective therapeutic strategies for GBM are urgently needed, particularly those that can overcome biological barriers and enhance treatment efficacy.
Purpose of the Study:
- To develop and evaluate a novel therapeutic approach combining targeted chemotherapy with in vivo dendritic cell (DC)-targeted genetic immunization for glioblastoma.
- To assess the impact of this combined therapy on the overall survival (OS) of mice bearing orthotopic glioblastoma.
Main Methods:
- Liposomal formulations of novel nicotinylated amphiphiles were developed to deliver the signal transducer and activator of transcription 3 (STAT3) inhibitor, WP-1066, targeting orthotopic mouse glioblastoma.
- Mice received intravenous administration of WP-1066-loaded liposomes in combination with subcutaneous genetic immunization using a tyrosinase-related protein-2 (TRP-2) DNA vaccine targeting dendritic cells (DCs).
- Overall survival (OS) was compared between the combination therapy group and control groups receiving either targeted chemotherapy or genetic immunization alone.
Main Results:
- The combination therapy resulted in a marked enhancement of overall survival (OS) in orthotopic glioblastoma-bearing mice, exceeding 500% compared to the control group.
- Mice treated with either targeted chemotherapy (WP-1066 liposomes) or in vivo DC-targeted genetic immunization alone showed significantly less improvement in OS.
- The novel approach successfully targeted anticancer drugs to the brain and stimulated an immune response without requiring the isolation of autologous immune cells.
Conclusions:
- The combination of targeted chemotherapy using WP-1066-loaded liposomes and in vivo DC-targeted genetic immunization represents a potent strategy for combating glioblastoma.
- This preclinical study demonstrates significant synergistic effects between targeted chemotherapy and immunotherapy, offering a promising avenue for future human glioblastoma treatment.
- The described approach simplifies treatment by avoiding autologous immune cell isolation, paving the way for potential clinical translation.
