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These misfolded proteins trigger oxidative stress, disrupt cellular homeostasis, and ultimately lead to tissue dysfunction. Overcoming the limitations of conventional strategies, multifunctional nanoparticles have emerged as a promising solution for simultaneously detecting, monitoring, and modulating pathogenic protein aggregates, offering a synergistic approach to addressing the multifaceted challenges of protein misfolding diseases. This systematic review examined 85 relevant studies published between 2010 and 2025, identified through PubMed searches. Only experimental studies reporting multifunctional or dual\u2010functional nanoparticles for the theranostics of protein misfolding disorders were included. Data were narratively synthesized according to nanoparticle type, biomedical function, and therapeutic or diagnostic outcomes. 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Their multifunctional nature offers several advantages for precision nano\u2010theranostics in managing amyloidosis, though further translational studies are essential to establish scalability, safety, and long\u2010term clinical applicability.<\/jats:p>","DOI":"10.1002\/jbm.b.70106","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:25:56Z","timestamp":1780640756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multifunctional Nanoparticles for Theranostics of Protein Misfolding Diseases: A Systematic Review"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2199-993X","authenticated-orcid":false,"given":"Huraira","family":"Tariq","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Sciences School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology  Islamabad 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