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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Mol Pharm. Author manuscript; available in PMC Oct 3, 2012.
Published in final edited form as:
PMCID: PMC3185194

Synergistic Induction of Apoptosis in Brain Cancer Cells by Targeted Co delivery of siRNA and Anti-cancer drugs


Multiple dysregulated pathways in tumors necessitate targeting multiple oncogenic elements by combining orthogonal therapeutic moieties like short-interfering RNAs (siRNA) and drug molecules in order to achieve a synergistic therapeutic effect. In this manuscript, we describe the synthesis of cyclodextrin-modified dendritic polyamines (DexAMs) and their application as a multicomponent delivery vehicle for translocating siRNA and anticancer drugs. The presence of β-cyclodextrins in our DexAMs facilitated complexation and intracellular uptake of hydrophobic anticancer drugs-Suberoylanilide hydroxamic acid (SAHA) and Erlotinib, whereas the cationic polyamine backbone allowed for electrostatic interaction with the negatively charged siRNA. The DexAMs complexes were found to have minimal cytotoxicity over a wide range of concentrations and were found to efficiently deliver siRNA, thereby silencing the expression of targeted genes. As a proof-of concept, we demonstrated that upon appropriate modification with targeting ligands, we were able to simultaneously deliver multiple payloads -siRNA against oncogenic receptor, EGFRvIII and anti-cancer drugs (SAHA or erlotinib) efficiently and selectively to glioblastoma cells. Co-delivery of siRNA-EGFRvIII and SAHA/Erlotinib in glioblastoma cells was found to significantly inhibit cell proliferation and induce apoptosis, as compared to the individual treatments.

Keywords: RNA interference, co-delivery, cyclodextrins, SAHA, brain tumor cells, targeted delivery


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