The application of M₁₂L₂₄ nanocages as cell-specific siRNA delivery agents in vitro

Small interfering RNA (siRNA) therapeutics have shown tremendous potential for the treatment of a range of diseases, but there is still a need for novel siRNA delivery materials. Here, we introduce M₁₂L₂₄ cages as siRNA delivery agents. We used four functionalized building blocks to form M₁₂L₂₄ nanocages. Dynamic light scattering showed that well-defined 130 nm nanocage/siRNA assemblies formed with positive zeta potentials. Cell-specific siRNA-mediated green fluorescent protein (GFP) silencing, controlled by the metal used for nanocage formation, was obtained. A Pt₁₂L₂₄ nanocage was highly effective in delivering siRNA to U2OS cells but showed little efficiency for HeLa cells. The less stable Pd₁₂L₂₄ nanocage derived from the same building block displayed effective GFP silencing for HeLa cells but not for U2OS cells. The ease of preparation and the ability to tune the binding strength, together with the specific siRNA delivery efficiency depending on the building blocks and metals, show potential for future siRNA delivery applications.