Cu Single Atom Nanozyme Based High-Efficiency Mild Photothermal Therapy through Cellular Metabolic Regulation

Mengyu Chang; Zhiyao Hou; Man Wang; Ding Wen; Chunxia Li; Yuhui Liu; Yanli Zhao; Jun Lin

doi:10.1002/anie.202209245

Cu Single Atom Nanozyme Based High-Efficiency Mild Photothermal Therapy through Cellular Metabolic Regulation

Angew Chem Int Ed Engl. 2022 Dec 12;61(50):e202209245. doi: 10.1002/anie.202209245. Epub 2022 Nov 16.

Authors

Mengyu Chang^{1

2}, Zhiyao Hou^{3

4}, Man Wang^{1

5}, Ding Wen¹, Chunxia Li⁵, Yuhui Liu⁶, Yanli Zhao², Jun Lin¹

Affiliations

¹ State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
² School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
³ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, P. R. China.
⁴ The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, P. R. China.
⁵ Institute of Molecular Sciences and Engineering, Shandong University, Qingdao, 266237, P. R. China.
⁶ State Key Laboratory of Nuclear Resources and Environment, East China University of Technology, Nanchang, 330013 Jiangxi, P. R. China.

PMID: 36264713
DOI: 10.1002/anie.202209245

Abstract

Upregulation of heat shock proteins (HSPs) drastically compromises the treatment effect of mild photothermal therapy (PTT). Herein, we designed a polyporous Cu single atom nanozyme (Cu SAzyme) loaded with licogliflozin (LIK066) for HSP-silencing induced mild PTT. On one hand, LIK066 inhibits glucose uptake by shutting sodium-dependent glucose transporter (SGLT) "valve", effectively blocking the energy source for adenosine triphosphate (ATP) generation. Without sufficient energy, cancer cells cannot synthesize HSPs. On the other hand, Cu SAzyme presents extraordinary multienzyme activities to induce reactive oxygen species (ROS) storm formation, which can damage the existing HSPs in cancer cells. Through a two-pronged strategy of SGLT inhibitor and ROS storm, LIK066-loaded Cu SAzyme shows high efficiency for comprehensive removal of HSPs to realize mild PTT.

Keywords: Heat Shock Proteins; Mild Photothermal Therapy; Reactive Oxygen Species; Single Atom Nanozymes; Sodium-Dependent Glucose Transporter.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anhydrides
Cell Line, Tumor
Heat-Shock Proteins / metabolism
Humans
Neoplasms* / therapy
Photothermal Therapy*
Reactive Oxygen Species / metabolism
Sorbitol

Substances

licogliflozin
Reactive Oxygen Species
Anhydrides
Sorbitol
Heat-Shock Proteins