Covalent, Non-Covalent, Encapsulated Nanodrug Regulate the Fate of Intra- and Extracellular Trafficking: Impact on Cancer and Normal Cells

Sci Rep. 2017 Jul 25;7(1):6454. doi: 10.1038/s41598-017-06796-7.

Abstract

Drugs need to be designed to access the designated intracellular organelle compartments in order to maximize anticancer efficacy. This study identified that covalently conjugated, non-covalent polyethylene glycol coated and encapsulated nanodrugs selectively influence drug uptake, the intracellular and extracellular trafficking of cancer cells. The types of nano conjugation modulated intracellular dynamics associated with differential impact on anti-cancer efficacy, but also induced differential cytotoxicity on cancer versus normal cells. In conclusion, this study demonstrated the importance of selecting the appropriate type of nano-conjugation for delivering organelle specific, active chemotherapeutic agents through controlled intracellular trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biological Transport / drug effects*
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology
  • Drug Liberation
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Exocytosis / drug effects
  • Exosomes / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Multidrug Resistance-Associated Proteins / metabolism
  • Nanotubes, Carbon / chemistry*
  • Polyethylene Glycols / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Multidrug Resistance-Associated Proteins
  • Nanotubes, Carbon
  • Polyethylene Glycols
  • Doxorubicin
  • EGFR protein, human
  • ErbB Receptors
  • multidrug resistance-associated protein 1