Scientists have designed nanoparticles that release drugs in the presence of a class of proteins that enable cancers to metastasize. That is, they have engineered a drug delivery system so that the very enzymes that make cancers dangerous could instead guide their destruction. The research was published in the journal Advanced Materials.
The system takes advantage of a class enzymes called matrix metalloproteinases that many cancers make in abundance. MMPs chew through membranes, allowing cancer cells to escape to colonize other regions of the body, often with deadly consequences.
The researchers created tiny spheres packed with the anti-cancer drug paclitaxel (also known by the trade names Taxol and Onxal) and coated with a peptide shell. MMPs tear up that shell, releasing the drug. The shell fragments form a ragged mesh that holds the drug molecules near the tumor.
To package the drug into the spheres, the researchers had to add chemical handles. As it turns out, a group of atoms essential to the drug molecule's effectiveness, and also toxicity, made for a good attachment point. That means the drug was inactivated as it flowed through the circulatory system until it reached the tumor.
The protection allowed the researchers to safely give a dose 16 times higher than they could with the formulation now used in cancer clinics, in a test in mice with grafted in fibrosarcoma tumors.
In additional preliminary tests, the researchers were able to halt the growth of the tumors for a least two weeks, using a single lower dose of the drug. In mice treated with the nanoparticles coated with peptides that are impervious to MMPs or given saline, the tumors grew to lethal sizes within that time.
The researchers will test the delivery system in other models, with other classes of drugs. They will also continue to modify the shell, to provide even greater protection and avoid uptake by organs such as liver, spleen and kidneys.
Based on material originally posted by University of California - San Diego.