TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy

Theranostics. 2020 May 25;10(15):6987-7001. doi: 10.7150/thno.44569. eCollection 2020.

Abstract

Adenosine triphosphate (ATP), as a key substance for regulating tumor progression in the tumor microenvironemnt (TME), is an emerging target for tumor theranostics. Herein, we report a minimalist but versatile nanoplatform with simultaneously TME-responsive drug release, TME-enhanced imaging, ATP-depletion sensitized chemotherapy and photothermal therapy for intelligent tumor theranostics. Methods: The Fe3+ and tannic acid (TA) coordination were self-deposited on doxorubicin (Dox) in a facile method to prepare Dox-encapsulated nanoparticles (DFTNPs). Results: When irradiated by a near infrared laser, the DFTNPs could elevate the temperature in the tumor region efficiently. Subsequently, the Dox could be released by the disassembly of Fe3+/TA in the TME to initiate chemotherapy. Particularly, the smart nanoagent not only enabled ATP-depletion and enhanced the therapeutic effect of chemotherapy, but also acted as photothermal transduction agent for photothermal therapy. Moreover, the nanoagent also acted as T1-weighted MR imaging,photoacoustic imaging and photothermal imaging contrast agent. The mice treated by DFTNPs plus laser showed a complete tumor eradication in 14d observation. Conclusion: This as-prepared versatile nanoplatform offers new insights toward the application of smart nanoagents for improved tumor theranostics.

Keywords: adenosine triphosphate; anti-tumor therapy; chemosensitivity; multimodal imaging; responsive drug release; synergistic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Drug Synergism*
  • Female
  • Humans
  • Iron / chemistry
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Photothermal Therapy / methods*
  • Tannins / chemistry
  • Topoisomerase II Inhibitors / pharmacology
  • Tumor Microenvironment / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Tannins
  • Topoisomerase II Inhibitors
  • Doxorubicin
  • Adenosine Triphosphate
  • Iron