Hydrolytically Stable Cationic Bis-MPA Dendrimers as Efficient Transfectants for Glioblastoma Cells and Primary Astrocytes
We report the biological evaluation of bis-MPA dendrimers terminated with either cysteamine (CYS) or 2-(dimethylamino)ethanethiol (DA) groups for siRNA transfection. The results show that aggregation phenomena are critical to the biological performance of these constructs. Confocal and 2D microscopy...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Castilla-La Mancha |
| Repositorio: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/47222 |
| Acceso en línea: | https://doi.org/10.1021/acs.biomac.5c01202 https://hdl.handle.net/10578/47222 https://pubs.acs.org/doi/full/10.1021/acs.biomac.5c01202 |
| Access Level: | acceso abierto |
| Palabra clave: | Cancer Dendrons Gene delivery Genetics Toxicity |
| Sumario: | We report the biological evaluation of bis-MPA dendrimers terminated with either cysteamine (CYS) or 2-(dimethylamino)ethanethiol (DA) groups for siRNA transfection. The results show that aggregation phenomena are critical to the biological performance of these constructs. Confocal and 2D microscopy demonstrated that only the G3-CYS dendrimer transported siRNA into cells. Accordingly, G3-CYS-mediated siRNA transfection reduced intracellular levels of the target proteins─p42-MAPK, Rheb, and MGMT─to 15–25% of control levels in a human glioblastoma cell line and mouse astrocytes. G3-CYS transfection efficiency was similar to that of commercial transfectants. However, its self-degradable bis-MPA backbone and tunable peripheral groups render it markedly superior, making it a promising transfection agent and emphasize the critical balance between structural design, biological efficacy, and safety. Despite its efficacy, G3-CYS displayed a narrow therapeutic window with pronounced cytotoxicity above 1 μM. In vivo studies further confirmed dose-dependent systemic toxicity, likely associated with enhanced blood coagulation. |
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