Facile Synthesis of Fe-Based Metal-Quinone Networks for Mutually Enhanced Mild Photothermal Therapy and Ferroptosis

Zhendong Liu; Sainan Liu; Bin Liu; Qi Meng; Meng Yuan; Xinyu Ma; Jiwei Wang; Meifang Wang; Kai Li; Ping'an Ma; Jun Lin

doi:10.1002/anie.202414879

Facile Synthesis of Fe-Based Metal-Quinone Networks for Mutually Enhanced Mild Photothermal Therapy and Ferroptosis

Angew Chem Int Ed Engl. 2024 Sep 26:e202414879. doi: 10.1002/anie.202414879. Online ahead of print.

Authors

Zhendong Liu^{1

2}, Sainan Liu¹, Bin Liu^{1

3}, Qi Meng^{1

2}, Meng Yuan^{1

2}, Xinyu Ma^{1

2}, Jiwei Wang^{1

2}, Meifang Wang¹, Kai Li¹, Ping'an Ma^{1

2}, Jun Lin^{1

2}

Affiliations

¹ State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
² School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.
³ College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China.

PMID: 39325096
DOI: 10.1002/anie.202414879

Abstract

Mild photothermal therapy (MPTT) has emerged as a promising therapeutic modality for attenuating thermal damage to the normal tissues surrounding tumors, while the heat-induced upregulation of heat shock proteins (HSPs) greatly compromises the curative efficacy of MPTT by increasing cellular thermo-tolerance. Ferroptosis has been identified to suppress the overexpression of HSPs by the accumulation of lipid peroxides and reactive oxygen species (ROS), but is greatly restricted by overexpressed glutathione (GSH) in tumor microenvironment and undesirable ROS generation efficiency. Herein, a synergistic strategy based on the mutual enhancement of MPTT and ferroptosis is proposed for cleaving HSPs to recover tumor cell sensitivity. A facile method for fabricating a series of Fe-based metal-quinone networks (MQNs) by coordinated assembly is proposed and the representative FTP MQNs possess high photothermal conversion efficiency (69.3 %). Upon 808 nm laser irradiation, FTP MQNs not only trigger effective MPTT to induce apoptosis but more significantly, potentiate Fenton reaction and marked GSH consumption to boost ferroptosis, and the reinforced ferroptosis effect in turn can alleviate the thermal resistance by declining the HSP70 defense and reducing ATP levels. This study provides a valuable rationale for constructing a large library of MQNs for achieving mutual enhancement of MPTT and ferroptosis.

Keywords: GSH depletion; ferroptosis; heat shock proteins; metal-quinone networks; mild photothermal therapy.

Abstract

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