A U87-EGFRvIII cell-specific aptamer mediates small interfering RNA delivery

Area of Science:

• Biotechnology
• Molecular Biology
• Cancer Research

Background:

• U87-EGFRvIII cells overexpress epidermal growth factor receptor variant III (EGFRvIII), a target in glioblastoma.
• Targeted delivery of therapeutic agents like small interfering RNA (siRNA) is crucial for glioblastoma treatment.

Purpose of the Study:

• To investigate the efficacy of a DNA aptamer, selected via cell-SELEX, as a carrier for delivering c-Met siRNA into U87-EGFRvIII cells.
• To evaluate the aptamer's ability to silence c-Met gene expression and impact glioblastoma cell proliferation and apoptosis.

Main Methods:

• A biotinylated DNA aptamer (BA) was selected against U87-EGFRvIII cells using cell-SELEX.
• BA was coupled to biotinylated c-Met siRNA via streptavidin for targeted delivery.
• Gene silencing was assessed by Western blotting for c-Met protein levels.
• Cell proliferation and apoptosis were evaluated using MTT and Annexin V/propidium iodide assays, respectively.

Main Results:

• The BA-c-Met siRNA conjugate significantly reduced c-Met protein expression in U87-EGFRvIII cells, comparable to lipofection.
• A significant increase in apoptosis and inhibition of cell growth was observed in cells treated with BA-c-Met siRNA compared to controls.
• The results confirm successful targeted gene silencing mediated by the DNA aptamer.

Conclusions:

• The DNA aptamer selected through cell-SELEX serves as an efficient and targeted carrier for siRNA delivery.
• This aptamer-siRNA complex offers a novel strategy for targeted combination therapy in glioblastoma.
• The findings support the potential of aptamer-based therapeutics for cancer treatment.