Piezocatalytic 2D WS2 Nanosheets for Ultrasound-Triggered and Mitochondria-Targeted Piezodynamic Cancer Therapy Synergized with Energy Metabolism-Targeted Chemotherapy

Quan Truong Hoang, Kim Anh Huynh, Thuy Giang Nguyen Cao, Ji Hee Kang, Xuan Nghia Dang, Vasanthan Ravichandran, Han Chang Kang, Minjong Lee, Jong Eun Kim, Young Tag Ko, Tae Il Lee, Min Suk Shim

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Piezoelectric nanomaterials that can generate reactive oxygen species (ROS) by piezoelectric polarization under an external mechanical force have emerged as an effective platform for cancer therapy. In this study, piezoelectric 2D WS2 nanosheets are functionalized with mitochondria-targeting triphenylphosphonium (TPP) for ultrasound (US)-triggered, mitochondria-targeted piezodynamic cancer therapy. In addition, a glycolysis inhibitor (FX11) that can inhibit cellular energy metabolism is loaded into TPP- and poly(ethylene glycol) (PEG)-conjugated WS2 nanosheet (TPEG-WS2) to potentiate its therapeutic efficacy. Upon US irradiation, the sono-excited electrons and holes generated in the WS2 are efficiently separated by piezoelectric polarization, which subsequently promotes the production of ROS. FX11-loaded TPEG-WS2 (FX11@TPEG-WS2) selectively accumulates in the mitochondria of human breast cancer cells. In addition, FX11@TPEG-WS2 effectively inhibits the production of adenosine triphosphate. Thus, FX11@TPEG-WS2 exhibits outstanding anticancer effects under US irradiation. An in vivo study using tumor-xenograft mice demonstrates that FX11@TPEG-WS2 effectively accumulated in the tumors. Its tumor accumulation is visualized using in vivo computed tomography. Notably, FX11@TPEG-WS2 with US irradiation remarkably suppresses the tumor growth of mice without systemic toxicity. This study demonstrates that the combination of piezodynamic therapy and energy metabolism-targeted chemotherapy using mitochondria-targeting 2D WS2 is a novel strategy for the selective and effective treatment of tumors.

Original languageEnglish
Article number2300437
JournalAdvanced Materials
Volume35
Issue number18
DOIs
StatePublished - 4 May 2023

Bibliographical note

Publisher Copyright:
© 2023 Wiley-VCH GmbH.

Keywords

  • WS
  • glycolysis inhibition
  • mitochondria targeting
  • piezodynamic therapy
  • piezoelectricity

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