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 re...

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Detalhes bibliográficos
Autores: Rodríguez Clemente, Irene, Karpus, Andrii, Buendía, Ángel, Sztandera, Krzystof, Regulska, Elzbieta, Bignon, Jerome, Caminade, Anne-Marie, Romero Nieto, Carlos, Steinmetz, Anke, Mignani, Serge, Majoral, Jean-Pierre, Ceña, Valentín
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/47224
Acesso em linha:https://doi.org/10.1021/acs.biomac.5c00171
https://hdl.handle.net/10578/47224
Access Level:acceso abierto
Palavra-chave:Cells
Dendrons
Genetics
Phosphorus
Reaction mechanisms
Descrição
Resumo: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.