Embedding viral capsids into aggregated metallic nanoparticles improves adenovirus entry in various human cancer cells - Archive ouverte HAL
Poster De Conférence Année : 2024

Embedding viral capsids into aggregated metallic nanoparticles improves adenovirus entry in various human cancer cells

Résumé

Delivery of macromolecules or nano-objects by electrotransfer is an attractive procedure in many fields of biotechnology and gradually in therapeutics. When using low amplitude/long lasting electric pulses to facilitate adenovirus delivery into cancer cell lines, we previously showed an enhanced virus penetration, not directly resulting from pulse application nor to membrane modifications, but rather due to viral capsid interactions with aggregated metallic nanoparticles, released from energized electrodes. In this work, we have quantified the viral and metallic particles forming these complexes by nanoparticle tracking and Inductively Coupled Plasma-Atomic Emission Spectroscopy, respectively. The intimate structure of these complexes and their cell penetration were investigated by transmission electronic microscopy and confocal microscopy. The new properties conferred on viral capsids by aggregated metallic nanoparticles were further studied. We characterized their contribution to virus stability and to penetration of embedded viral capsids into cell lines derived from several human cancers, including some Head and Neck carcinoma cell lines poorly infected with adenovirus vectors. Using a panel of endocytosis inhibitors, we found that macropinocytosis is the main penetration pathway for the viral capsids associated with the metallic aggregates. The previous properties could be useful to reduce the virus doses required for tumor treatments with oncolytic adenoviruses and/or adenovirus-derived vectors expressing immunomodulatory protein(s). The modification of the virus stability and cell entry process might also modulate the quality and intensity of the immune response induced against the viral vector.
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vendredi 3 janvier 2025
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vendredi 3 janvier 2025
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Dates et versions

hal-04850030 , version 1 (19-12-2024)

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  • HAL Id : hal-04850030 , version 1

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Thierry Ragot, Catherine Pioche-Durieu, Tudor Manoliu, Angela Tesse, Catherine Brenner, et al.. Embedding viral capsids into aggregated metallic nanoparticles improves adenovirus entry in various human cancer cells. European Society of Gene and Cell Therapy (ESGCT) 2024, Oct 2024, ROME, Italy. Mary Ann Liebert, Inc, Human Gene Therapy. ⟨hal-04850030⟩
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