Role of Hydrophilic Monomers in α‐Tocopherol‐Based Copolymers in Causing Cell Death by ROS Production

Abstract

succinate (TOS) is known to induce cell death by intracellular production of reactive oxygen species (ROS). However, TOS is not enough for cancer target ability. This study is aimed to enhance the accumulation and cytotoxicity of TOS by designing random copolymers. Methacrylated -tocopheryl succinate (MTOS) is polymerized with three types of hydrophilic monomers to find appropriate hydrophilic monomer, in terms of particle size, self-assembled structure, cellular uptake, and cytotoxicity. N-Vinylpyrrolidone (VP), 2-methacryloyloxyethyl phosphocholine (MPC), and glycosyloxyethyl methacrylate (GEMA) are selected to prepare the copolymers, and their effect in forming polymeric assembly and cellular uptake are examined. Each hydrophilic monomer is copolymerized with MTOS to obtain random copolymers [poly(GEMA-ran-MTOS), poly(VP-ran-MTOS), and poly(MPC-ran-MTOS)]. The assembled nature is characterized in terms of particle size by dynamic light scattering and transmission electron microscopy: Size of the assembled copolymers increase with the mol% of MTOS. The cytotoxicity of the human cervical cancer cell line (HeLa cells) increases significantly after incubating with poly(GEMA-ran-MTOS) and poly(VP-ran-MTOS), whereas poly(MPC-ran-MTOS) do not affect the cell viability. Both the copolymers enhance the mitochondrial ROS generation in HeLa cells. Therefore, choice of hydrophilic monomers to copolymerize with MTOS dominates to enhance the accumulation and cytotoxicity of TOS.