ArticleNature biotechnology2025
Engineered platelets as targeted protein degraders and application to breast cancer models.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The research landscape and evolutionary trends of platelet-derived extracellular vesicles: a bibliometric and LDA analysis (2015-2026).Frontiers in oncology · 2026Pooled it
- Unlocking the "undruggable": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation.Drug delivery · 2026Review
- Organization from cell to tissue derived delivery systems for immunotherapy.Materials today. Bio · 2026Article
- Progress and challenges in traceless ligand-directed labelling chemistry.Communications chemistry · 2026Review
- Lysosome self-sorting nanodegraders for hepatic clearance of pathogenic serum mediators.Nature nanotechnology · 2026Article
- ESCRT-Mimetic Nanodegrader Targets STING for Anti-Inflammatory Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineering platelets as cancer therapeutics.Nature reviews. Clinical oncology · 2026Review
- Peptide-Based PROTACs: Transitioning from Static Paradigm to a Dynamic Landscape within Targeted Protein Degradation.Bioconjugate chemistry · 2026Review
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Targeting HSP90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications.Molecular cancer · 2026Review
- Proteolysis-targeting chimera (PROTAC) nanomedicines toward cancer treatment: From synthesis to therapeutic delivery.Biomaterials · 2026Review
- Thrombopoiesis meets tumorigenesis: unlocking the diagnostic and prognostic potential of platelet indices in breast cancer- a narrative review.Annals of medicine and surgery (2012) · 2026Review
- Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Platelet-engineered CAR-T cells as adjuvant therapy after cancer surgery.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The emerging roles of platelet-derived extracellular vesicles in disease.Annals of medicine · 2025Review
- Recent Advances in Nanomedicine: Cutting-Edge Research on Nano-PROTAC Delivery Systems for Cancer Therapy.Pharmaceutics · 2025Review
- Targeted protein degradation with small molecules for cancer immunotherapy.Asian journal of pharmaceutical sciences · 2025Review
- Targeted degradation of extracellular proteins: state of the art and diversity of degrader designs.Journal of hematology & oncology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
Abstract
Clinical application of chimeric molecules for targeted protein degradation has been limited by unfavorable drug-like properties and biosafety concerns arising from nonspecific biodistribution after systemic administration. Here we develop a method to engineer platelets for degradation of either intracellular or extracellular proteins of interest (POIs) in vivo by covalently labeling heat shock protein 90 (HSP90) in platelets with a POI ligand. The degrader platelets (DePLTs) target wound areas and undergo activation. Depending on the tethered POI ligand and transport mechanism of the prelabeled HSP90, activated DePLTs can mediate targeted protein degradation in the target cell through the ubiquitin-proteasome machinery or the lysosome. HSP90 packaged into platelet-derived microparticles uses the ubiquitin-proteasome system to degrade intracellular POIs, whereas released free HSP90 redirects extracellular POIs to lysosomal degradation. In postsurgical breast cancer mouse models, DePLTs engineered with corresponding POI ligands effectively degrade intracellular bromodomain-containing protein 4 or extracellular programmed cell death ligand 1, thereby suppressing cancer recurrence or metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.