pH-Activatable cell penetrating peptide dimers for potent delivery of anticancer drug to triple-negative breast cancer

J Control Release. 2021 Feb 10:330:898-906. doi: 10.1016/j.jconrel.2020.10.063. Epub 2020 Nov 2.

Abstract

We developed a pH-activatable cell-penetrating peptide dimer LH2 with histidine residues, which can penetrate cells, specifically in weak acidic conditions, even at few tens of nanomolar concentrations. LH2 effectively delivered paclitaxel into triple-negative breast cancer cells, MDA-MB-231, via formation of non-covalent complexes (PTX-LH2(M)) or covalent conjugates (PTX-LH2(C)). Moreover, LH2 showed prolonged circulation in the body and enhanced accumulation in tumors. Both PTX-LH2(M) and PTX-LH2(C) showed strong antitumor effects in a triple-negative breast cancer grafted mouse model at an extremely low dosage.

Keywords: Cancer; Cell penetrating peptide; Histidine; Paclitaxel; pH activatable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / therapeutic use
  • Breast Neoplasms*
  • Cell Line, Tumor
  • Cell-Penetrating Peptides* / therapeutic use
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Mice, Nude
  • Paclitaxel / therapeutic use
  • Pharmaceutical Preparations*
  • Triple Negative Breast Neoplasms* / drug therapy

Substances

  • Antineoplastic Agents
  • Cell-Penetrating Peptides
  • Pharmaceutical Preparations
  • Paclitaxel