2. Academic Validation
  3. Active-targeting biomimetic nanosystem for prostate cancer enhances radiotherapy efficacy by inducing ferroptosis

Active-targeting biomimetic nanosystem for prostate cancer enhances radiotherapy efficacy by inducing ferroptosis

  • J Nanobiotechnology. 2025 Nov 30;24(1):9. doi: 10.1186/s12951-025-03879-w.
Zhihao Hu 1,  Hongji Li 1,  Kai Gan 1,  Yu Li 2,  Yao Jiang 3,  Keying Zhang 1,  Zhengxuan Li 1,  Yike Zhou 1,  Tong Lu 1,  Chao Xu 1,  Shaojie Liu 1,  Limin He 1,  Fa Yang 1,  Jun Jiang 1,  Hongtao Song 1,  Ying Wang 1,  Li Guo 4,  Changhong Shi 5,  Weihong Wen 6,  Donghui Han 7,  Weijun Qin 8
Affiliations

Affiliations

  • 1 Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
  • 2 Department of Urology, Daping Hospital, Army Medical University, Chongqing, 400042, China.
  • 3 Department of Urology, Air Force 986 Hospital, Xi'an, 710054, China.
  • 4 The Tenth Outpatient Department, Air Force 986 Hospital, Xi'an, 710054, China.
  • 5 Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, Xi'an, 710032, China.
  • 6 Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, China. [email protected].
  • 7 Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. [email protected].
  • 8 Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. [email protected].
PMID: 41318491 DOI: 10.1186/s12951-025-03879-w
Abstract

Radioresistance and off-target toxicity remain major challenges in prostate Cancer (PCa) radiotherapy. Here, we report a biomimetic nanoplatform (Au/MOF-FIN@M-gy1) that synergistically enhances radiation deposition and Ferroptosis for precision radiosensitization. By engineering macrophage membranes with prostate-specific membrane antigen (PSMA)-targeting nanobodies (gy1), we achieve tumor-selective delivery of Au/MOF nanoparticles preloaded with Ferroptosis inducers (FINs). Upon lysosomal release, FINs disrupt redox homeostasis via GPX4 suppression, while Au/MOF amplifies radiation-induced Reactive Oxygen Species (ROS), collectively triggering lethal lipid peroxidation cascades. This dual mechanism is further demonstrated to elicit radiosensitizing effects in both bone-metastatic and radio-refractory PCa models without requiring radiation dose escalation, thereby improving the therapeutic index. Our study demonstrates a nanoparticle-enabled strategy to enhance tumor-specific radiotherapy by dual-targeting metabolic vulnerabilities.

Keywords

Ferroptosis; Membrane-coated nanoparticles; Prostate cancer; Prostate-specific membrane antigen; Radiation therapy; Targeted therapy.

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