In a review of nanoparticles for cancer therapy and imaging, the authors describe the challenges and future of the technology. A major dilemma is how to design nanoparticles that travel to the tumor and kill it without harming healthy tissue. The solution can be summarized in one word: targeting. Targeting usually exploits tumor biology, and active targeting usually requires conjugation of a ligand to a drug, such as one that recognizes a tumor marker.

On the other hand, passive targeting typically does not require conjugation of a ligand to a drug. For example, nanoparticles can be made in certain sizes that tumors will preferentially absorb — a phenomenon known as the enhanced permeability and retention effect. Or a drug can be conjugated to a molecule that will be cleaved by enzymes in cancer cells, activating the drug. Alternatively, drugs can be delivered directly via injections or surgical procedures, limiting the spread of the drug to the tumor area. However, invasive procedures are undesirable and, in some cases, unfeasible.

Targeting also means ensuring that the nanoparticles avoid problems caused by the human body. The liver and spleen will try to remove the nanoparticles, the outer tissue of organs will serve as a barrier to them, and the aqueous environment is not compatible with many cancer drugs, most of which are insoluble in water.

Besides targeting, the future entails enabling nanoparticles to release sufficient amounts of drugs and making the nanoparticles multifunctional. For example, the same nanoparticles that treat tumors also will target the tumors and enable doctors to visualize them. Such nanoparticles may provide information about prognosis and response to therapy by identifying tumor markers. Eventually, the drugs will have to undergo toxicity testing and be standardized and manufactured per the FDA. (Expert Review of Anticancer Therapy, June 2007, pp. 833-837.)