2.B.50. The Triphenylphosphonium Cation-Tocopheryl Polyethylene Glycol Succinate Conjugate (TPP-TPGS) Family
Singh et al. 2019 have synthesized a nanocarrier using tocopheryl polyethylene glycol succinate (TPGS) conjugated to triphenylphosphonium cation" (TPP-TPGS) for improving the efficacy of doxorubicin (DOX). TPP has affinity for an elevated mitochondrial transmembrane potential gradient, which is usually high in cancer cells. Owing to its structural similarity to mitochondrially directed anticancer compounds of the "tocopheryl succinate" family, TPP-TPGS interferes with mitochondrial CII enzyme activity, increases intracellular oxidative stress, and induces apoptosis of breast cancer cells. TPP-TPGS inhibits the drug efflux transporter, P glycoprotein (PgP), which, along with greater cell uptake and inherent cytotoxic activity of TPP-TPGS, cumulatively results in a 3-fold increment in anticancer activity of DOX as well as greater induction of necroapoptosis and growth arrest. After intravenous administration in mice with breast cancer, DTPP-TPGS accumulated preferentially in tumor tissues, producing greater antitumor activity compared to DOX alone (Singh et al. 2019).