Active-targeting biomimetic nanosystem for prostate cancer enhances radiotherapy efficacy by inducing ferroptosis
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.
Authors
- Yao Jiang (ORCID: https://orcid.org/0000-0002-4934-0941)
- Hongji Li (ORCID: https://orcid.org/0009-0005-7694-1880)
- Shaojie Liu (ORCID: https://orcid.org/0000-0002-8140-1185)
- Changhong Shi (ORCID: https://orcid.org/0000-0001-6771-2481)
- Weihong Wen (ORCID: https://orcid.org/0000-0003-4739-4871)
- Tong Lü (ORCID: https://orcid.org/0000-0001-5691-9209)
- Donghui Han (ORCID: https://orcid.org/0000-0002-3742-4355)
- Kai Gan (ORCID: https://orcid.org/0000-0001-8414-7242)
- Jun Jiang (ORCID: https://orcid.org/0000-0002-5971-3174)
- Yu Li (ORCID: https://orcid.org/0000-0001-6910-5933)
- Chao Xu (ORCID: https://orcid.org/0000-0001-5520-4834)
- Yue Zhou
- Hongtao Song
- Zhengxuan Li (ORCID: https://orcid.org/0000-0001-9907-1543)
- Keying Zhang (ORCID: https://orcid.org/0000-0002-7888-7938)
- Zhihao Hu (ORCID: https://orcid.org/0000-0003-1558-9105)
- Guo Li (ORCID: https://orcid.org/0000-0002-5742-4432)
- Limin He (ORCID: https://orcid.org/0009-0004-4527-8222)
- Weijun Qin (ORCID: https://orcid.org/0009-0000-4794-3565)
- Fa Yang
Institutions
- Army Medical University (CN)
- Northwestern Polytechnical University (CN)
- People 's Liberation Army 451 Hospital (CN)
- Daping Hospital (CN)
- Xijing Hospital (CN)
- Air Force Medical University (CN)
Publication Details
- Journal
- Journal of Nanobiotechnology
- Published
- 2025-11-30
- DOI
- https://doi.org/10.1186/s12951-025-03879-w
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 0.00