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Chitosan-Based Nanoparticles for Intracellular Delivery of ISAV Fusion Protein cDNA into Melanoma Cells: A Path to
Claudia Robles-Planells1,2,3, Giselle Sánchez-Guerrero1,2, Carlos Barrera-Avalos1
1Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile (USACH), Alameda, 3363 Santiago, Chile.
Abstract:
Oncolytic virus therapy has been tested against cancer in preclinical models and clinical assays. Current evidence shows that viruses induce cytopathic effects associated with fusogenic protein-mediated syncytium formation and immunogenic cell death of eukaryotic cells. We have previously demonstrated that tumor cell bodies generated from cells expressing the fusogenic protein of the infectious salmon anemia virus (ISAV-F) enhance crosspriming and display prophylactic antitumor activity against melanoma tumors. In this work, we evaluated the effects of the expression of ISAV-F on the B16 melanoma model, both in vitro and in vivo, using chitosan nanoparticles as transfection vehicle. We confirmed that the transfection of B16 tumor cells with chitosan nanoparticles (NP-ISAV) allows the expression of a fusogenically active ISAV-F protein and decreases cell viability because of syncytium formation in vitro. However, the in vivo transfection induces a delay in tumor growth, without inducing changes on the lymphoid populations in the tumor and the spleen. Altogether, our observations show that expression of ISAV fusion protein using chitosan nanoparticles induces cell fusion in melanoma cells and slight antitumor response.
Insights
Chitosan nanoparticles delivered the infectious salmon anemia virus (ISAV) fusion protein into melanoma cells, causing cell fusion and a slight delay in tumor growth. This study explores ISAV-F
Area of Science:
- Oncology
- Virology
- Nanotechnology
- Immunology
Background:
- Oncolytic virus therapy utilizes viruses to induce cancer cell death via cytopathic effects, syncytium formation, and immunogenic cell death.
- Previous research demonstrated that tumor cells expressing the infectious salmon anemia virus (ISAV) fusogenic protein (ISAV-F) exhibit antitumor activity.
Purpose of the Study:
- To evaluate the effects of ISAV-F expression in the B16 melanoma model.
- To assess the efficacy of chitosan nanoparticles as a transfection vehicle for ISAV-F delivery.
- To investigate the in vitro and in vivo anti-melanoma potential of ISAV-F expression.
Main Methods:
- Transfection of B16 melanoma cells with chitosan nanoparticles carrying the ISAV-F gene (NP-ISAV).
- In vitro assessment of ISAV-F expression, cell viability, and syncytium formation.
- In vivo evaluation of tumor growth and lymphoid population changes in tumor-bearing mice.
Main Results:
- Successful transfection of B16 cells with NP-ISAV resulted in the expression of fusogenically active ISAV-F.
- In vitro studies showed decreased cell viability due to syncytium formation.
- In vivo transfection led to a delay in tumor growth but did not significantly alter lymphoid populations in the tumor or spleen.
Conclusions:
- Expression of the ISAV fusion protein via chitosan nanoparticles induces melanoma cell fusion.
- This approach demonstrates a slight antitumor response in vivo, suggesting potential for oncolytic applications.
- Further research is needed to optimize this strategy for enhanced therapeutic efficacy.
