Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization

Changhao Li; Cairong Xiao; Lizhen Zhan; Zhekun Zhang; Jun Xing; Jinxia Zhai; Zhengnan Zhou; Guoxin Tan; Jinhua Piao; Yahong Zhou; Suijian Qi; Zhengao Wang; Peng Yu; Chengyun Ning

Bioactive Materials (Dec 2022)

Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization

Changhao Li,
Cairong Xiao,
Lizhen Zhan,
Zhekun Zhang,
Jun Xing,
Jinxia Zhai,
Zhengnan Zhou,
Guoxin Tan,
Jinhua Piao,
Yahong Zhou,
Suijian Qi,
Zhengao Wang,
Peng Yu,
Chengyun Ning

Affiliations

Changhao Li: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China
Cairong Xiao: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China
Lizhen Zhan: School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China
Zhekun Zhang: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China
Jun Xing: School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China
Jinxia Zhai: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China
Zhengnan Zhou: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China
Guoxin Tan: School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China
Jinhua Piao: School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China
Yahong Zhou: CAS Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Science, Beijing, 100190, China
Suijian Qi: School of Food Science and Engineering, South China University of Technology, Guangzhou, 510641, China; Corresponding author. School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
Zhengao Wang: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China; China-Singapore International Joint Research Institute, Guangzhou, 511365, China; Corresponding author. School of Material Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
Peng Yu: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China; China-Singapore International Joint Research Institute, Guangzhou, 511365, China; Corresponding author. School of Material Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
Chengyun Ning: School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Metallic Materials Surface Functionalization Engineering Research Center of Guangdong Province, South China University of Technology, Guangzhou, 510641, China; China-Singapore International Joint Research Institute, Guangzhou, 511365, China

Journal volume & issue: Vol. 18
pp. 399 – 408

Abstract

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Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not fully effective and limited by the development of resistance. Herein, inspired by the intervention of endogenous bioelectricity in vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable of breaking bioelectric homeostasis within cells, to achieve tumor vascular normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity pulsed ultrasound. We demonstrated that wireless electrical stimulation significantly inhibited endothelial cell migration and differentiation in vitro. Interestingly, we found that the angiogenesis-related eNOS/NO pathway was inhibited, which could be attributed to the destruction of the intracellular calcium ion gradient by wireless electrical stimulation. In vivo tumor-bearing mouse model indicated that wireless electrical stimulation normalized tumor vasculature by optimizing vascular structure, enhancing blood perfusion, reducing vascular leakage, and restoring local oxygenation. Ultimately, the anti-tumor efficacy of combination treatment was 1.8 times that of the single chemotherapeutic drug doxorubicin group. This work provides a wireless electrical stimulation strategy based on the mechano-electrical conversion performance of piezoelectric nanoparticles, which is expected to achieve safe and effective clinical adjuvant treatment of malignant tumors.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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