The micelles penetrate the cell membrane in a different way, entering the cell through a process called endocytosis. Small sections of the cell membrane pinch off and form bubble-like vesicles that engulf the micelles. These membrane-enclosed sacks travel along the cell’s internal transport system until they approach the nucleus. As the micelles get closer to the cell nucleus the chemistry inside the vesicles gradually becomes more acidic, the better to digest their cargo into small nutrient particles.
As conditions become more acidic, the molecules of the micelles, which have self-assembled around the drug molecules, lose their ability to stick together and release the drug molecules.
“Micelles work as nanoscaled Trojan horses to efficiently deliver a drug into the nucleus of drug-resistant cancer cells,” says lead author Kazunori Kataoka, a professor in the Department of Materials Engineering and Bioengineering at the University of Tokyo.
This drug-delivery mechanism slowed tumor growth by approximately 75 percent compared with tumors treated with regular oxaliplatin.
By equipping each micelle component with a green fluorescent tag at the surface and a red fluorescent tag that faces the core, the researchers were able to track their progress through cells with fluorescent video microscopy and film when and where the micelles delivered their payload.
Katakoka’s colleague Nobuhiro Nishiyama, says the micelles are more responsive than any other known drug carrier to the chemical conditions at the target site inside a cell.
Omid Farokhzad of the Laboratory of Nanomedicine and Biomaterials at Harvard Medical School says that without this kind of subcellular targeting system, drugs delivered by nanocarriers are not necessarily more effective. “Nanocarrier engineering really needs to become more sophisticated, and people will look to this work as a landmark study for how you can engineer the system to target subcellular compartments,” Farokhzad says.