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Nanoparticle encapsulation enables systemic IGF-Trap delivery to inhibit intracerebral glioma growth
Yinhsuan Michely Chen1, Julien Chambon2, Alexandre Moquin
1Department of Medicine, Division of Experimental Medicine, McGill University.
Background:
Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma. We previously reported that the intracerebral growth of glioma cells with reduced IGF-1R levels was inhibited. The objectives of this study were to evaluate the sensitivity of glioma cells to a novel IGF-axis inhibitor, the IGF-Trap, and optimize its delivery to the brain.
Methods:
We tested the effect of the IGF-Trap on the growth of the human glioma stem cells MES-1123 and U87 MG cells, and of murine GL261 cells in vivo, using subcutaneous and orthotopic implantation.
Results:
We show that the growth of glioma cells implanted subcutaneously or orthotopically in the brain was inhibited by systemic and direct intracerebral administration of IGF-Trap, respectively, resulting in increased survival. To increase the efficiency of systemic delivery to the brain, we encapsulated the IGF-Trap in trimethyl chitosan (TRIOZAN™) nanoparticles prior to intravenous injection. We found that nanoparticle encapsulation increased the uptake and retention of the IGF-Trap in the brain and resulted in an improved therapeutic effect against intra-cerebrally growing tumors.
Conclusion:
Our results identify the IGF-Trap as a potent inhibitor of intracerebral glioma growth and show that encapsulation in nanoparticles can improve delivery of biologics such as the IGF-Trap to the brain, thereby enhancing the therapeutic response.
Insights
A novel IGF-Trap drug effectively inhibited glioblastoma growth. Encapsulating this drug in nanoparticles improved its delivery to the brain, enhancing therapeutic effects against brain tumors.
Area of Science:
- Neuro-oncology
- Drug Delivery Systems
- Cancer Therapeutics
Background:
- Glioblastoma is an aggressive brain cancer with poor prognosis.
- The blood-brain barrier limits treatment efficacy for brain tumors.
- Insulin-like Growth Factor 1 Receptor (IGF-1R) is a potential therapeutic target for glioblastoma.
Purpose of the Study:
- To assess the efficacy of a novel IGF-axis inhibitor, the IGF-Trap, against glioma.
- To optimize the brain delivery of the IGF-Trap.
Main Methods:
- Tested IGF-Trap efficacy on human and murine glioma cells in vitro and in vivo (subcutaneous and orthotopic models).
- Investigated systemic and direct intracerebral administration of IGF-Trap.
- Encapsulated IGF-Trap in trimethyl chitosan (TRIOZAN™) nanoparticles for enhanced brain delivery via intravenous injection.
Main Results:
- IGF-Trap inhibited glioma cell growth and increased survival in both subcutaneous and orthotopic models.
- Nanoparticle encapsulation significantly improved IGF-Trap uptake and retention in the brain.
- Encapsulated IGF-Trap demonstrated enhanced therapeutic effects against intracerebral tumors.
Conclusions:
- The IGF-Trap is a potent inhibitor of intracerebral glioma growth.
- Nanoparticle formulation enhances brain delivery of biologics like IGF-Trap.
- This approach improves therapeutic response for brain tumors.
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