Modern cancer drugs known as nanomedicines may be less effective in younger patients, whose livers are able to filter a significant amount of the medication out of the bloodstream, keeping it from reaching tumors, studies in mice suggest.
“Our liver is designed to protect us (from toxins in the blood), but for young people it might also be protecting them in a way that limits the effectiveness of nanotherapies,” study leader Dr. Wen Jiang of The University of Texas MD Anderson Cancer Center in Houston said in a statement.
Nanomedicines use minuscule particles to carry the drugs. Advantages can include reduced toxicity, increased target specificity, and safe delivery of higher dosages.
In laboratory experiments, Jiang’s team administered the same dosages of nanodrug formulations of the chemotherapies paclitaxel or doxorubicin to young and old mice with breast tumors.
In the older mice, treatment led to better tumor control because the animals’ livers had fewer of the filtering cells, known as Kupffer cells, that trap drugs and toxins, so more of the drug could reach the tumor, according to a report published on Monday in Nature Nanotechnology.
Blocking the activity of a specific protein present to a greater extent in Kupffer cells of younger livers reduced filtering of the medication and improved the drugs’ therapeutic effectiveness, but only in the younger mice, the researchers also found.
“These results show that there may not always be a one-size-fits-all drug delivery strategy that is effective across diverse patient populations, and that personalized design is warranted in future nanomedicines,” Jiang said.
Roughly 100 nano-based therapies have been approved by U.S. and European regulators. While this study focused on cancer, filtering by the liver represents a potential hurdle for all nanodrugs, Jiang said.
