Abstract

Auristatin PE (PE) as an anti-microtubule agent possesses good anticancer activity. However, the poor target effect and strong side effect limit its clinical applications. Targeted delivery of PE may overcome the disadvantages associated with PE, being very conducive to continuing clinical trials of PE. Boron nitride nanotubes (BNNTs) with unique physical and chemical properties have attracted considerable attention in drug delivery. Herein, a targeted drug delivery strategy based on folate-conjugated boron nitride nanotubes (BNNTs-FA) was used to improve the efficacy of PE. It was found that PE was successfully loaded onto BNNTs-FA via π-π stacking and hydrogen bonding interactions. [email protected] exhibited stronger cytotoxicity to Hep G2 cells than free PE and [email protected] complexes due to the increased cellular uptake of PE mediated by the FA receptor. [email protected] showed excellent antiproliferative activities in a dose- and time-dependent manner. Furthermore, [email protected] induced apoptosis of Hep G2 cells via an intrinsic mitochondria–mediated pathway by reducing the mitochondrial membrane potential, activating Caspase-9 and Caspase-3. The construction of [email protected] system successfully improves the target effect of PE and may be very promising for the treatment of liver cancer in the future.