Two-Step Delivery Method Ups Cancer Drug’s Concentration In Tumors

Researchers report that a two-step procedure—delivering a tumor-localizing, drug-absorbing nanoparticle followed by the actual therapeutic—increases the amount of drug that reaches tumor cells and the time the drug acts on cells (Sci. Rep. 2016, DOI: 10.1038/srep18720).

Mark W. Grinstaff of Boston University, Yolonda Colson of Brigham & Women’s Hospital, and coworkers first administered a polymer-based nanoparticle to mice with tumors. This nanoparticle swells and becomes a gel in mildly acidic surroundings. Because cancer cells are more acidic than normal cells, the tiny particles expanded to 10 times their original size inside tumors and became trapped.

Two days later, the researchers gave the mice Taxol (paclitaxel), which concentrated inside the trapped nanoparticles because of its hydrophobicity. Taxol concentrations within the mouse tumors rose to about five times the level attained when researchers gave mice the drug alone. The drug also remained in the tumor longer, giving Taxol more time to kill cancer cells.

When Grinstaff, Colson, and coworkers delivered nanoparticles preloaded with Taxol to mice with cancer, orders of magnitude more drug got to the tumors than was achieved with the two-step procedure. This might be expected because the drug doesn’t have to find the nanoparticles in the body.

But the new approach has an advantage: Nanomedicines preloaded with drugs would be considered new drug entities by the Food & Drug Administration and would have to pass a full series of clinical trials. Empty nanoparticles, on the other hand, are defined by FDA as medical devices because they do not have chemistry-based therapeutic activity. Taxol is also already FDA-approved. So the two-step strategy could minimize drug approval complications and expenses.

Cancer nanomedicine expert Joseph M. DeSimone of the University of North Carolina, Chapel Hill, notes that the study “reports a first-of-its-kind result” because the two-step treatment requires neither selective binding interactions between drug and nanoparticle nor an activating event to make the drug start working, either or both of which were required in earlier drug-nanoparticle treatments.