Bi₂ S₃ -Tween 20 Nanodots Loading PI3K Inhibitor, LY294002, for Mild Photothermal Therapy of LoVo Cells In Vitro and In Vivo.

Abstract

Although various types of photothermal agents are developed for photothermal cancer therapy, relatively few photothermal agents exhibit high tumor inhibition rate under relatively mild conditions. Herein, a multifunctional Bi₂ S₃ -Tween 20 nanoplatform loaded with PI3K inhibitor LY294002 is designed as a novel photothermal agent for inhibitor and photothermal synergistic therapy of tumors under mild photothermal therapy conditions. The LY294002 of PI3K inhibitor, after being loaded by Bi₂ S₃ -Tween 20 nanodots, exhibits greatly increased drug utilization and reduced side effects on normal tissues. In vivo, Bi₂ S₃ -Tween 20@LY294002 upon near-infrared 808 nm laser irradiation shows potent antitumor activity under relatively mild conditions (power density: 0.6 W cm^-2 ). Moreover, the mechanism studies also demonstrate that Bi₂ S₃ -Tween 20@LY294002 potently kills LoVo cancer cells under low-power near-infrared light irradiation, by downregulating the expression of heat shock protein 70 (HSP70) so as to increase the sensitivity of tumor cell hyperthermia and activating BAX/BAK-regulated mitochondrial apoptosis pathway. The results demonstrate that the newly synthesized multifunctional nanoplatform paves a new avenue for accurate therapy of photothermal-resistant cancer.