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However, the clinical translation of TPD agents remains hampered by their inherent physicochemical limitations, including poor solubility, membrane impermeability, and lack of tissue selectivity. Nanotechnology offers a strategic pathway to overcome these barriers. This review examines the convergence of TPD and nanotechnology, highlighting how diverse nanoplatforms\u2014ranging from lipid and polymeric nanoparticles to inorganic carriers and biomimetic systems\u2014can address fundamental delivery challenges. We discuss key design strategies such as physical encapsulation, chemical conjugation, and carrier\u2010free self\u2010assembly between nanocarrier\u2010assisted TPD\u2014where nanoparticles improve degrader pharmacokinetics\u2014and nanostructure\u2010integrated TPD\u2014where the nanoscaffold directly participates in ternary complex formation, and explore how engineering the nano\u2010bio interface enables precise control over cellular uptake, intracellular trafficking, and ternary complex formation. We also critically assess current translational hurdles, including manufacturing complexity, biosafety concerns, and tumor heterogeneity, while offering perspectives on how rational design and interdisciplinary collaboration can accelerate clinical adoption. By reimagining protein degraders as components of intelligent nano\u2010systems, nano\u2010TPD holds the potential to transform undruggable targets into actionable therapeutic opportunities.<\/jats:p>","DOI":"10.1002\/smtd.70928","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T06:13:22Z","timestamp":1785996802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanotechnology\u2010Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges"],"prefix":"10.1002","volume":"10","author":[{"given":"Haoran","family":"Zhu","sequence":"first","affiliation":[{"name":"The MOE Key Laboratory of Spectrochemical Analysis &amp; Instrumentation the Key Laboratory of Chemical Biology of Fujian Province State Key Laboratory of Physical Chemistry of Solid Surfaces Department of Chemical Biology College of Chemistry and Chemical Engineering Xiamen University  Xiamen 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