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

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.

Clickable X-ray Nanoprobes for Nanoscopic Bioimaging of Cellular Structures

“…The nanoparticles were modified with azide groups and chelated Co 2+ to prepare the Click-XRN Co with an average particle size of 119.9 nm, which had enough localization accuracy for micrometer-sized mitochondria. As a mitochondria-targeting agent, TPP has demonstrated the capacity to effectively integrate diverse functional molecules and produce delocalized positive charges, affording it the capability to traverse the hydrophobic double-layer membrane of mitochondria. − At present, as lipophilic cations, TPP has been widely used in the development of fluorogenic probes for detecting mitochondrial biomarkers, demonstrating its efficacy in specifically targeting mitochondria. ,, …”

Highly Biocompatible Polyester-Based Piezoelectric Elastomer with Antitumor and Antibacterial Activity for Ultrasound-Enhanced Piezoelectric Therapy

“…Remarkably, compared with traditional PTT, ultrasound (US)-triggered piezoelectric therapy based on piezoelectric materials has raised considerable interest in cancer therapy owing to its advantages of high-selectivity, noninvasiveness, and negligible toxicity, − which holds a good potential for future clinical translation. The piezoelectric material could induce charge migration and separation under external stimulation, , further reacting with water to generate highly cytotoxic reactive oxygen species (ROS). This innovative therapeutic paradigm is capable of responding to external mechanical stimuli to generate surface electric potentials, thus achieving a mechanoelectric transition while avoiding adverse effects in healthy tissues, which will have positive impacts on both tumor therapy and tissue repair after surgical resection.…”

Recent advancements in piezoelectric energy harvesting for implantable medical devices

“…Figure 4 shows the possible applications of PEH for implantable medical devices. The various applications of the PEH for IMDs are drug delivery (Gabrielsson et al, 2021), pacemaker (Kabir et al, 2022), dental implant (Park et al, 2020), in vivo diagnosis & treatment (Zhang et al, 2022b), cancer Therapy (Truong Hoang et al, 2023), repair of nerve tissue (Wu et al, 2022), neuro regulation (Guan et al, 2023), acoustic transmitter (Jiang et al, 2022), bariatric (Dagdeviren et al, 2017), cochlear implant (İlik et al, 2018), knee implant (Safaei et al, 2018) and myriad (Sun et al, 2019) to quote a few.…”