Acid-controlled release complexes of podophyllotoxin and etoposide with acyclic cucurbit[n]urils for low cytotoxicity

Bioorg Med Chem. 2019 Feb 1;27(3):525-532. doi: 10.1016/j.bmc.2018.12.035. Epub 2018 Dec 28.

Abstract

The targeted or responsive systems are appealing therapeutic platforms for the development of next-generation precision medications. So, we design and prepare acid-controlled release complexes of podophyllotoxin (POD) and etoposide (VP-16) with pH-labile acyclic cucurbit[n]urils, and their characteristics and inclusion complexation behaviors were investigated via fluorescence spectroscopy, nuclear magnetic resonance and X-ray power diffraction. Cells incubated with complexes have been analyzed by high-content analysis (HCA), and cytotoxicity tests have been completed by MTT assay. The results showed that complexes with different binding constants can release the drug substance in the physiological pH environment of cancer cells, maintain good anticancer activity, and have low cytotoxicity. This provides a strategy about targeted and responsive systems of POD and VP-16 for clinical application.

Keywords: Acid-controlled release; Acyclic cucurbit[n]uril; Inclusion complex; Low cytotoxicity; Podophyllotoxin and etoposide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Etoposide / chemistry
  • Etoposide / pharmacology*
  • HEK293 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Macrocyclic Compounds / chemistry
  • Macrocyclic Compounds / pharmacology*
  • Molecular Structure
  • Optical Imaging
  • Podophyllotoxin / chemistry
  • Podophyllotoxin / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Macrocyclic Compounds
  • cucurbit(n)uril
  • Etoposide
  • Podophyllotoxin