ACS Nano: Oxygen-Deficient Tungsten Oxide (WOx) Nanobelts with pH-Sensitive Degradation for Enhanced Sonodynamic Therapy of Cancer

Title：

Oxygen-Deficient Tungsten Oxide (WO_x) Nanobelts with pH-Sensitive Degradation for Enhanced Sonodynamic Therapy of Cancer

Authors：

Yangkai Zhou^1,3#, Nailin Yang^1#, Fei Gong¹, Yuanjie Wang¹, Xiaoyuan Yang¹, Yizhi Dai^1,3, Qiao Yu¹, Li Wang¹, Weifan Chen⁴, Mingpeng Zhuo^1,2*, and Liang Cheng¹*

Institutions：

¹Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China

²College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China

³University of Chinese Academy of Sciences, Beijing 100190, China

⁴School of Materials Science & Engineering, Nanchang University, Nanchang 330031, China

Abstract：

The further bioapplications of sonodynamic therapy (SDT) were hindered by the inadequate efficiency and poor degradability of sonosensitizers and the hypoxic tumor microenvironment (TME). Therefore, it is ideal to develop pH-sensitive sonosensitizers that generate abundant reactive oxygen species (ROS) and rapidly degrade in a neutral environment while slowly degrading in an acidic environment to reduce their long-term toxicity. Herein, the defective tungsten oxide nanobelts (WO_x NBs) were developed as a type of pH-sensitive and biodegradable sonosensitizers with a high SDT efficiency and low toxicity for enhanced SDT. The defective oxygen sites of WO_x NBs could inhibit the recombination of electrons and holes, making WO_x NBs promising sonosensitizers that could generate abundant ROS under ultrasound (US) irradiation. Enhanced by the catalase (CAT) that reacted with H₂O₂ to generate O₂, the WO_x NBs exhibited better SDT performance against 4T1 cells in both normoxic and hypoxic environments. In addition, the WO_x NBs could degrade by releasing protons (H⁺), resulting in intracellular acidification and inhibited cell motility that further enhanced the therapeutic effects of SDT. Assisted with CAT and ALG for hypoxia refinement and better retention, the WO_x NBs enabled effective SDT and antimetastasis against 4T1 tumors in vivo. Most importantly, the WO_x NBs could degrade rapidly in normal tissues but slowly in an acidic TME, which was favorable for their fast clearance, without any obvious long-term toxicity. Our work developed defective WO_x NBs with a high SDT efficiency and pH-sensitive degradation for enhanced SDT, which extended the biomedical application of tungsten-based nanomaterials and the further development of SDT.

IF：

18.027

Link：

https://pubs.acs.org/doi/full/10.1021/acsnano.2c07903