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

作者：Xiao Hu, Fei Li, Xin-Hang Qian, Yusen Zhang, Shuai Ke, Yunxia Jin, Shuai Yuan, Yuanyuan Zhang, Rui Li, Lei Cao, Lang Rao, Xian‐Tao Zeng, Lingling Zhang · 发表于：Nano Research · 年份：2025 · DOI：10.26599/nr.2025.94907314 · 被引用次数：6 · 研究领域：Ferroptosis and cancer prognosis、Cancer, Lipids, and Metabolism、Nanoplatforms for cancer theranostics

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 + /Cu 2+ 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.