Anti-cancer activity of camptothecin nanocrystals decorated by silver nanoparticles

Abstract

The emergence of multidrug resistant cancer phenotypes dramatically attenuates the efficiency of a variety of anti-cancer drugs. Silver nanoparticles (AgNPs) display excellent anti-cancer activity and dramatic inhibitory effect on drug resistance related proteins like P-glycoprotein (Pgp). Here we developed a novel drug nanocrystal formulation of Camptothecin (CPT), a broad spectrum anti-cancer agent, decorated by AgNPs. The resulting combinational formulation of CPT and AgNPs, named as CPT/Ag nanocrystals, demonstrated excellent dispersion properties and an improved dissolution rate, drug stability and cellular uptake rate. Because CPT nanocrystals are able to bypass Pgp recognition and AgNPs inhibit both Pgp expression and activity, CPT/Ag nanocrystals showed extreme and indiscriminate cytotoxicity against a variety of both drug sensitive and drug resistant cancer cells. Moreover, the quickly and plenty of released CPT from the CPT/Ag nanocrystals triggered by the tumor microenvironment led to a relaxed and cleavable chromatin structure, facilitating DNA damage and apoptotic potential of AgNPs that were subsequently released.