Encapsulation of Apoptotic Proteins in Lipid Nanoparticles to Induce Death of Cancer Cells

Abstract

According to previous reports, cationic nanoparticles (cNPs) consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), a cationic lipid, without any cargos, induce generation of reactive oxygen species (ROS) and toxicity in cells. We investigated the effect of DOTAP-based cNPs containing encapsulated human pro-apoptotic proteins (P-cNPs), tBid, Bax, or cytochrome c (Cyt c) on the death of HepG2, cancer cells. Upon the treatment to cells, cNPs containing Cyt c-cargo were the most effective in inducing cell death, followed by tBid- and Bax-cNPs. Among three P-cNPs, Cyt c-cNPs also induced the highest levels of ROS production and caspase-3 activity in the cells under the treatment with the same DOTAP concentration. The incorporation of dioleoylglycerol (DOG), a neutral phospholipid, in cNPs at the expense of DOTAP resulted in an increased amount of the encapsulated protein and consequently enhanced cell death in a DOG concentration-dependent manner. Thus, the present cNP formulation with protein cargo may elicit apoptotic effects in cancer cells and serve as a rational background for the preparation of cationic lipid-based NP formulation for cancer treatment.