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Despite many antiamyloid strategies, most suffer from poor selectivity, limited potency, and inadequate biocompatibility. Here, we report the first demonstration that polymeric Janus nanorods (JNRs) can delay both oligomerization and fibrillation of hIAPP through high\u2010affinity, sequence\u2010specific interactions. These anisotropic poly(N, N\u2010dimethylacrylamide) nanostructures, synthesized via reversible addition fragmentation chain transfer polymerization, self\u2010assemble to display a \u03b2\u2010hairpin mimetic ligand (LP2) on one face, enabling multivalent and directional binding. Biophysical assays reveal that JNR\u2010LP2 suppresses amyloid aggregation at substoichiometric concentrations, markedly outperforming free LP2 and nonfunctionalized JNRs. Mechanistic studies, including capillary zone electrophoresis and Thioflavin T fluorescence, show that JNR\u2010LP2 stabilizes monomeric hIAPP, prevents oligomer formation, and delays fibril nucleation. Importantly, binding experiments provide the first quantitative evidence of a strong affinity constant between a polymeric nanoparticle and hIAPP, establishing molecular specificity with negligible off\u2010target activity against unrelated amyloid proteins such as Tau. In cellular models, JNR\u2010LP2 mitigates hIAPP\u2010induced cytotoxicity while exhibiting excellent intrinsic biocompatibility. Collectively, these findings identify JNRs as a modular and selective nanoplatform for amyloid inhibition, offering a novel precision\u2010nanomedicine approach to T2DM.<\/jats:p>","DOI":"10.1002\/smsc.70326","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:05:38Z","timestamp":1785146738000},"source":"Crossref","is-referenced-by-count":0,"title":["Janus Polymeric Nanorods Inhibit human Amylin Oligomerization and Fibrillation for Potential Type 2 Diabetes Treatment"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9685-8709","authenticated-orcid":false,"given":"Mathilde","family":"J\u00e9go","sequence":"first","affiliation":[{"name":"Institut Galien Paris\u2010Saclay, UMR 8612 CNRS Universit\u00e9 Paris\u2010Saclay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Kalem","sequence":"additional","affiliation":[{"name":"Institut des Mol\u00e9cules et Mat\u00e9riaux du 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