A Polymeric Nanosponge as a Broad-Spectrum Reactive Oxygen Species Scavenger for Acute Kidney Injury Treatment

Shan He; Chaoran Chen; Fangzheng Li; Wenxuan Xu; Dongdong Li; Ming Liang; Xianzhu Yang

doi:10.1021/acs.nanolett.3c02531

A Polymeric Nanosponge as a Broad-Spectrum Reactive Oxygen Species Scavenger for Acute Kidney Injury Treatment

Nano Lett. 2023 Oct 11;23(19):8978-8987. doi: 10.1021/acs.nanolett.3c02531. Epub 2023 Sep 19.

Authors

Shan He¹, Chaoran Chen^{2

3}, Fangzheng Li^{2

3}, Wenxuan Xu^{2

3}, Dongdong Li⁴, Ming Liang⁴, Xianzhu Yang^{4

2

3}

Affiliations

¹ School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China.
² School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong 511442, P. R. China.
³ National Engineering Research Center for Tissue Restoration and Reconstruction, Guangdong Provincial Key Laboratory of Biomedical Engineering, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China.
⁴ Department of Nephrology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China.

PMID: 37726233
DOI: 10.1021/acs.nanolett.3c02531

Abstract

Acute kidney injury (AKI) is closely associated with the overproduction of reactive oxygen species (ROS), which can cause multiple organ dysfunctions without timely treatment. However, only supportive treatments are currently available for AKI in clinics. Here, we developed nanomaterials of hyperbranched polyphosphoester (PPE) containing abundant thioether (S-PPE NP) and thioketal bonds (TK-PPE NP). Our data demonstrates that S-PPE NP exhibits an excellent capability of absorbing and scavenging multiple types of ROS, including H₂O₂, •OH, and •O₂^-, via thioether oxidation to sulfone or sulfoxide; it was also determined that S-PPE NP efficiently eliminates intracellular ROS, thus preventing cellular damage. Moreover, S-PPE NP was able to efficiently accumulate in the injured kidneys of AKI-bearing mice. As a result, the administration of S-PPE NP provided a superior therapeutic effect in AKI-bearing mice by downregulating ROS- and inflammation-related signaling pathways, thus reducing cell apoptosis. This thioether-containing polymer represents a promising broad-spectrum ROS scavenger that can be used for effective AKI treatments.

Keywords: acute kidney injury; broad-spectrum ROS scavenger; nanosponge; polyphosphoester; thioether-containing polymer.