Triggered Release Enhances the Cytotoxicity of Stable Colloidal Drug Aggregates

ACS Chem Biol. 2019 Jul 19;14(7):1507-1514. doi: 10.1021/acschembio.9b00247. Epub 2019 Jun 25.

Abstract

Chemotherapeutics that self-assemble into colloids have limited efficacy above their critical aggregation concentration due to their inability to penetrate intact plasma membranes. Even when colloid uptake is promoted, issues with colloid escape from the endolysosomal pathway persist. By stabilizing acid-responsive lapatinib colloids through coaggregation with fulvestrant, and inclusion of transferrin, we demonstrate colloid internalization by cancer cells, where subsequent lapatinib ionization leads to endosomal leakage and increased cytotoxicity. These results demonstrate a strategy for triggered drug release from stable colloidal aggregates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Antineoplastic Agents, Hormonal / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colloids / chemistry*
  • Delayed-Action Preparations / chemistry*
  • Drug Liberation
  • Endosomes / metabolism
  • Fulvestrant / administration & dosage*
  • Fulvestrant / pharmacokinetics
  • Fulvestrant / pharmacology
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Transferrin / chemistry

Substances

  • Antineoplastic Agents, Hormonal
  • Colloids
  • Delayed-Action Preparations
  • Transferrin
  • Fulvestrant