Streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular and tumor delivery of enzymes

J Control Release. 2018 Jun 28:280:1-10. doi: 10.1016/j.jconrel.2018.04.051. Epub 2018 Apr 30.

Abstract

Despite the extremely high substrate specificity and catalytically amplified activity of enzymes, the lack of efficient cellular internalization limits their application as therapeutics. To overcome this limitation and to harness enzymes as practical biologics for targeting intracellular functions, we developed the streptavidin-mirror DNA tetrahedron hybrid as a platform for intracellular delivery of various enzymes. The hybrid consists of streptavidin, which provides a stoichiometrically controlled loading site for the enzyme cargo and an L-DNA (mirror DNA) tetrahedron, which provides the intracellular delivery potential. Due to the cell-penetrating ability of the mirror DNA tetrahedron of this hybrid, enzymes loaded on streptavidin can be efficiently delivered into the cells, intracellularly expressing their activity. In addition, we demonstrate tumor delivery of enzymes in an animal model by utilizing the potential of the hybrid to accumulate in tumors. Strikingly, the hybrid is able to transfer the apoptotic enzyme specifically into tumor cells, leading to strong suppression of tumor growth without causing significant damage to other tissues. These results suggest that the hybrid may allow anti-proliferative enzymes and proteins to be utilized as anticancer drugs.

Keywords: Cancer therapy; DNA tetrahedron; Enzyme delivery; Streptavidin-mirror DNA tetrahedron hybrid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Biological Transport
  • Caspase 3 / chemistry*
  • Caspase 3 / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytoplasm / drug effects
  • DNA / chemistry*
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Humans
  • Mice, Inbred BALB C
  • Neoplasms / drug therapy*
  • Streptavidin / chemistry*
  • Tissue Distribution / drug effects

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • DNA
  • Streptavidin
  • Caspase 3