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Research Article | Open Access

Mild photothermal therapy-enhanced nano-ferroptosis inducer for potent treatment of advanced prostate cancer

Xiao Hu1,2,§, Fei Li1,§, Xin-Hang Qian1,§, Yu-Sen Zhang1, Shuai Ke1, Yun-Xia Jin4, Shuai Yuan1, Yuan-Yuan Zhang1, Rui Li5, Lei Cao2, Lang Rao2, Xian-Tao Zeng1,3 (), Ling-Ling Zhang1 ()
Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules & College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China
Xinjiang Key Laboratory of Solid State Physics and Devices, School of Physics Science and Technology, Xinjiang University, Urumqi 830017, China

§ Xiao Hu, Fei Li, and Xin-Hang Qian contributed equally to this work.

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In this work, mesoporous polydopamine nanoparticles (MPDA NPs) were developed to simultaneously deliver Cu+/Cu2+ ion pairs and glutathione peroxidase 4 inhibitor RSL3 to tumor sites, whose antitumor effect was tumor-specific and enhanced by mild photothermal therapy. We hope this work could provide nanomedicine scientists and clinicians with a reasonable paradigm for developing novel therapies for advanced prostate cancer.

Abstract

Androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSis) often have limited efficacy in patients with advanced prostate cancer (PCa) (especially AR-negative). Inducing ferroptosis in PCa cells is an attractive therapeutic approach. In this work, mesoporous polydopamine nanoparticles (MPDA NPs) were developed to simultaneously deliver Cu+/Cu2+ ion pairs and glutathione peroxidase 4 (GPX4) inhibitor RSL3 to tumor sites for enhanced treatment of PCa. The prepared MPDA-Cu-RSL3@HA (MPCRH) NPs induced ferroptosis by promoting lipid peroxidation and regulating phospholipid profiles in PCa cells, and the above effects were further enhanced by mild photothermal therapy (mPTT) without damaging normal tissues. mPTT can promote reactive oxygen species (ROS) generation and degrade tumor extracellular matrix in vivo to promote nanodrugs intratumoral penetration. In short, this work shows the great application potential of mPTT-enhanced nano-ferroptosis inducers in the field of PCa treatment, in order to provide a reasonable paradigm for nanodrug development and PCa treatment.

Keywords

prostate cancerferroptosismild photothermal therapychemodynamic therapymesoporous polydopamine

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Nano Research
Volume 18 Issue 4,
April 2025
Article number: 94907314
DOI: 10.26599/NR.2025.94907314
Cite this article:
Hu X, Li F, Qian X-H, et al. Mild photothermal therapy-enhanced nano-ferroptosis inducer for potent treatment of advanced prostate cancer. Nano Research, 2025, 18(4): 94907314. https://doi.org/10.26599/NR.2025.94907314
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