Gefitinib, a drug used for treatment of cancers, has been found to have enhanced anti-cancer properties when delivered encapsulated inside nanoparticles. The difference in property arises from the fact that the nanoparticle-covered drug acts as a 'histone acetyltransferase' rather than a 'tyrosine kinase inhibitor', which gefitinib is in its free form, new research says1.
Gefitinib is a widely used drug for treatment of non-small cell lung cancer (NSCLC). It is a tyrosine kinase inhibitor, meaning it inhibits the enzymes tyrosine kinases, responsible for triggering cancer signals. Researchers have now shown that gefitinib behaves as a histone acetyltransferase (HAT) activator when coated in poly lactic-co-glycolic acid (PLGA) nanoparticles.
The new complex — nano-gefitinib — exhibits completely different anti-cancer mechanism as compared to the free drug, which stalls cell proliferation primarily by inhibiting the Epidermal Growth Factor Receptor (EGFR).
The researchers evaluated the molecular mechanism behind this enhanced activity. They found that the nanoparticles "hyperacetylate the histone H3 via activation of histone acetyltransferases p300/CBP, which further increases the expression of cell cycle arrest protein p21."
"We were intrigued to observe that a tyrosine kinase inhibitor behaved as HAT activator merely by choosing a nano-sized transporting vehicle," says Kulbhushan Tikoo, lead researcher from the National Institute of Pharmaceutical Education and Research, Mohali. The findings suggest that the activity of drugs may completely change when they are delivered in nano form, he told Nature India.