ArticleSignal transduction and targeted therapy2025
In vivo self-assembled nano-PROTAC for the dual degradation of AR and HSP90 to overcome castration-resistant prostate cancer resistance.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- HSP90 shields ROC1/RBX1 from proteasomal degradation by CHIP E3 ubiquitin ligase to promote lung adenocarcinoma.Signal transduction and targeted therapy · 2026Article
- Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Delivering Degradation: Nanomedicine and Programmable Proximity Platforms for Targeted Protein Degradation.Pharmaceutics · 2026Review
- Autonomously Motile Nano-PROTACs Act as Protein-Sweeping Robots to Enhance Targeted Protein Degradation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Living Inorganic Nanomaterials: Design, Preparation, and Biomedical Applications.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Gliovirin-like Alkaloids with Spirocyclic Skeletons from the Mangrove Endophytic FungusMarine drugs · 2026Article
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Therapeutic translation of traditional Chinese medicine Huangqi derived exosome like nanoparticles: targeting prostate cancer through ferroptosis activation, immune reprogramming, and microbiome modulation.Journal of nanobiotechnology · 2026Article
- Daidzein-engineered high-accumulation self-therapeutic nanoplatform drives androgen receptor degradation via ubiquitination-proteasome system to overcome enzalutamide resistance in castration-resistant prostate cancer.Materials today. Bio · 2026Article
- Exploiting Oxidative Stress as Achilles' Heel: From Redox Homeostasis to Ferroptosis in Prostate Cancer.Antioxidants (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Castration-resistant prostate cancer demonstrates intrinsic or acquired resistance to second-generation androgen-targeted therapies, posing a challenge in clinical treatment. In this study, on the basis of in vivo self-assembly nanotechnology, we designed a PSMA-targeted nano-PROTAC with a proximity degradation effect. Nano-PROTAC not only precisely degrades the AR receptor but also cleverly degrades the HSP90 that is closely bound to the AR receptor, utilizing the spatial distance self-adaptive characteristics of its nanostructure. In the 22Rv1 cell model, Nano-PROTAC degraded 80% of the AR protein and 65% of the HSP90 protein. More importantly, nano-PROTAC could degrade 74% of the AR splice variant AR-V7 protein, showing the potential ability to overcome drug resistance. We further constructed an enzalutamide-resistant xenograft tumor mouse model to evaluate the therapeutic effect of the Nano-PROTAC. Compared with the combination treatment group of AR and HSP90 inhibitors (enzalutamide and pimitespib), the nano-PROTAC treatment group presented a high tumor growth inhibition value of up to 78% and a median survival extension of 15 days. Nano-PROTACs that simultaneously degrade AR and HSP90 can overcome the resistance of prostate cancer to PSMA- and AR-positive castration-resistant prostate cancer, except for neuroendocrine prostate cancer, which provides a new therapeutic strategy for the treatment of prostate cancer.
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