A Telomerase-Responsive DNA Icosahedron for Precise Delivery of Platinum Nanodrugs to Cisplatin-Resistant Cancer

Angew Chem Int Ed Engl. 2018 May 4;57(19):5389-5393. doi: 10.1002/anie.201801195. Epub 2018 Apr 14.

Abstract

A telomerase-responsive DNA icosahedron was designed to precisely release caged platinum nanodrugs into cisplatin-resistance tumor cells for effective therapy. This DNA icosahedron was constructed from two pyramidal DNA cages connected with telomerase primers and telomeric repeats, and platinum nanodrugs were then encapsulated into the DNA structure. In the presence of telomerase, the primers are extended, leading to inner-chain substitution of the DNA icosahedron and subsequent release of the caged nanodrugs. This DNA icosahedron can precisely release caged nanodrugs in response to telomerase in tumor cells, giving enhanced anticancer efficacy in drug-resistant carcinoma and with reduced toxicity to normal tissues. We speculate that this precisely designed, well controlled DNA cage could be generalized to diverse anticancer drugs.

Keywords: DNA nanotechnology; antitumor agents; controlled release; drug resistance; telomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • DNA / chemistry
  • DNA / metabolism*
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Metal Nanoparticles / chemistry*
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Particle Size
  • Platinum / chemistry*
  • Surface Properties
  • Telomerase / metabolism*

Substances

  • Antineoplastic Agents
  • Platinum
  • DNA
  • Telomerase
  • Cisplatin