Selective targeting of tumor and stromal cells by a nanocarrier system displaying lipidated cathepsin B inhibitor

Angew Chem Int Ed Engl. 2014 Sep 15;53(38):10077-81. doi: 10.1002/anie.201402305. Epub 2014 Jun 27.

Abstract

Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC-NS-629) is described. Ex vivo and in vivo studies confirmed selective targeting and internalization of LNC-NS-629 by tumor and stromal cells, thus validating CtsB targeting as a highly promising approach to cancer diagnosis and treatment.

Keywords: cancer; cathepsin B; drug delivery; theranostics; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin B / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / pathology
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Female
  • Mammary Neoplasms, Experimental / diagnosis
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mice
  • Molecular Structure
  • Nanostructures / chemistry*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Structure-Activity Relationship

Substances

  • Cysteine Proteinase Inhibitors
  • Drug Carriers
  • Doxorubicin
  • Cathepsin B