3D melanoma cocultures as improved models for nanoparticle-mediated delivery of RNA to tumors
Cancer therapy is an emergent application for mRNA therapeutics. While in tumor immunotherapy, mRNA encoding for tumor-associated antigens is delivered to antigen-presenting cells in spleen and lymph nodes, other therapeutic options benefit from immediate delivery of mRNA nanomedicines directly to t...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
17 March 2022
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| In: |
Cells
Year: 2022, Volume: 11, Issue: 6, Pages: 1-13 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells11061026 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cells11061026 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2073-4409/11/6/1026 
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| Author Notes: | Maximilian E.A. Schäfer, Florian Keller, Jens Schumacher, Heinrich Haas, Fulvia Vascotto, Ugur Sahin, Mathias Hafner and Rüdiger Rudolf |
| Summary: | Cancer therapy is an emergent application for mRNA therapeutics. While in tumor immunotherapy, mRNA encoding for tumor-associated antigens is delivered to antigen-presenting cells in spleen and lymph nodes, other therapeutic options benefit from immediate delivery of mRNA nanomedicines directly to the tumor. However, tumor targeting of mRNA therapeutics is still a challenge, since, in addition to delivery of the cargo to the tumor, specifics of the targeted cell type as well as its interplay with the tumor microenvironment are crucial for successful intervention. This study investigated lipoplex nanoparticle-mediated mRNA delivery to spheroid cell culture models of melanoma. Insights into cell-type specific targeting, non-cell-autonomous effects, and penetration capacity in tumor and stroma cells of the mRNA lipoplex nanoparticles were obtained. It was shown that both coculture of different cell types as well as three-dimensional cell growth characteristics can modulate distribution and transfection efficiency of mRNA lipoplex formulations. The results demonstrate that three-dimensional coculture spheroids can provide a valuable surplus of information in comparison to adherent cells. Thus, they may represent in vitro models with enhanced predictivity for the in vivo activity of cancer nanotherapeutics. |
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| Item Description: | Gesehen am 30.04.2024 |
| Physical Description: | Online Resource |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells11061026 |