siRNA Interaction and Transfection Properties of Polycationic Phosphorus Dendrimers
Glioblastoma multiforme (GBM) is the most common type of primary brain tumor in adults and has a poor prognosis. Small interfering RNA (siRNA) can disrupt different mechanisms involved in the genesis of several diseases including GBM. However, siRNA complexation with nonviral cationic carriers is required to transport siRNAs inside cells and promote its function. We have designed and synthesized new cationic phosphorus dendrimers bearing either 6, 12, or 24 pyrrolidinium or piperidinium groups on their surface. These dendrimers bound siRNA, those bearing terminal pyrrolidinium having the highest affinity. However, they showed marked differences in protecting siRNA from RNase-mediated degradation. Molecular modeling suggested that, beyond the overall protonation status, the intrinsic flexibility and individual binding properties of these dendrimers contributed to the modulation of biological profiles. However, these phosphorus dendrimers were unable to transport significant amounts of siRNA into GBM cells and, accordingly, transfection was inefficient.
Authors
- Krzysztof Sztandera (ORCID: https://orcid.org/0000-0001-7595-7198)
- Jean‐Pierre Majoral (ORCID: https://orcid.org/0000-0002-0971-817X)
- Ángel M. López-Buendía (ORCID: https://orcid.org/0000-0002-0431-2744)
- Jérôme Bignon (ORCID: https://orcid.org/0000-0002-6294-9671)
- Carlos Romero‐Nieto (ORCID: https://orcid.org/0000-0002-3472-933X)
- Andrii Karpus (ORCID: https://orcid.org/0000-0002-5760-3086)
- Anke Steinmetz (ORCID: https://orcid.org/0000-0002-0856-4295)
- Elżbieta Regulska (ORCID: https://orcid.org/0000-0003-0054-8802)
- Serge Mignani (ORCID: https://orcid.org/0000-0002-1383-5256)
- Anne‐Marie Caminade (ORCID: https://orcid.org/0000-0001-8487-3578)
- Valentı́n Ceña (ORCID: https://orcid.org/0000-0001-8928-3681)
- Irene Rodríguez-Clemente
Institutions
- Centre National de la Recherche Scientifique (FR)
- Instituto de Salud Carlos III (ES)
- Sanofi (France) (FR)
- Normandie Université (FR)
- Laboratoire de Chimie de Coordination (FR)
- Universidade da Madeira (PT)
- University of Castilla-La Mancha (ES)
- Université de Caen Normandie (FR)
Publication Details
- Journal
- Biomacromolecules
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1021/acs.biomac.5c00171
- Citations
- 3
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Agência Regional para o Desenvolvimento da Investigação, Tecnologia e Inovação
- European Commission
- Ministerio de Ciencia, Tecnología e Innovación Productiva
- Centre National de la Recherche Scientifique
- Universidad de Castilla-La Mancha
- Junta de Comunidades de Castilla-La Mancha
- European Research Council
- Fundação para a Ciência e a Tecnologia
- Agencia Estatal de Investigación