• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
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
NIHMSID: NIHMS317342

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

Abstract

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...