The Apoptosis of Liver Cancer Cells Promoted by Curcumin/TPP-CZL Nanomicelles With Mitochondrial Targeting Function
Wanyu Li, Yanan Chen, Kun He, Tianshou Cao, Daibo Song, Huiling Yang, Li Li, Jiantao Lin
Abstract
The mitochondrion is one of the most important cellular organelles, and many drugs work by acting on mitochondria. Curcumin (Cur)-induced apoptosis of HepG2 in liver cancer cells is closely related to the function of inhibiting mitochondria. However, the mitochondrion-targeting curcumin delivery system was rarely been reported. It is important to develop a high-efficiency mitochondrion-targeting curcumin vector that can deliver curcumin into mitochondria directly. Here, a special mitochondrion-targeting delivery system based on triphenylphosphine bromide (TPP)-chitosan-g-poly-(N-3-carbobenzyloxy- l -lysine) (CZL) with TPP functional on the surface is designed to perform highly efficient mitochondria-targeting delivery for effective liver cancer cell killing in vitro . The TEM images showed that the nanomicelles were spherical; the results of fluorescence test showed that TPP-CZL nanomicelles could promote the cellular uptake of drugs and finally targeted to the mitochondria. The results of cell survival rate and Hoechst staining showed that curcumin/TPP-CZL nanomicelles could promote the apoptosis of liver cancer cells. Curcumin/TPP-CZL nanomicelles could significantly reduce the mitochondrial membrane potential, increase the expression of pro apoptotic protein Bcl-2, and reduce the expression of antiapoptotic Bax protein, and these results were significantly better than curcumin/CZL nanomicelles and curcumin. It is a potential drug delivery system with high efficiency to target mitochondria of liver cancer cells.