Huixin He and Tamara Minko led a team of investigators from academia and industry that used porous silica nanoparticles to deliver to cancer cells a traditional anticancer drug together with a therapeutic small interfering RNA (siRNA) molecule. Doxorubicin, the anticancer drug, kills tumors by triggering a form of cell death known as apoptosis, while the siRNA the researchers used suppresses the production of the protein Bcl-2, which malignant cells produce to stop apoptosis.
To create this two-for-one therapeutic, the investigators first load doxorubicin into the pores of silica nanoparticles and then coat the nanoparticle with spherical polymer nanoparticles known as dendrimers. The dendrimer-coated nanoparticles bind tightly to siRNA molecules, creating the novel therapeutic. When administered to multidrug resistance ovarian cancer cells, the nanoparticle formulation was over 130 times more lethal to the cells than was free doxorubicin. Most of this increase in anticancer activity resulted from the effects of the siRNA therapy.
The researchers noted, however, that since the nanoparticle uptake appears to be endocytosis mediated, and the doxorubicin delivered into the nucleus and perinuclear region of the cell, it is likely that this therapeutic approach is also able to bypass the pump mechanism cancer cells use to remove drugs that enter the cell via diffusion pathways. The researchers also found that the nanoparticles release very little of their doxorubicin payload outside of the cells, suggesting that the nanoparticle-based therapy might reduce the side effects associated with doxorubicin treatment.