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                <title level="j">Biomacromolecules</title>
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                <term xml:lang="en">Cells</term>
                <term xml:lang="en">Dendrons</term>
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                <term xml:lang="en">Phosphorus</term>
                <term xml:lang="en">Reaction mechanisms</term>
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              <p>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.</p>
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