Janus Polymeric Nanorods Inhibit human Amylin Oligomerization and Fibrillation for Potential Type 2 Diabetes Treatment
Abstract
Protein misfolding and aggregation of human islet amyloid polypeptide (hIAPP) are central to β-cell dysfunction in type 2 diabetes mellitus (T2DM). 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-affinity, sequence-specific interactions. These anisotropic poly(N, N-dimethylacrylamide) nanostructures, synthesized via reversible addition fragmentation chain transfer polymerization, self-assemble to display a β-hairpin mimetic ligand (LP2) on one face, enabling multivalent and directional binding. Biophysical assays reveal that JNR-LP2 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-LP2 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-target activity against unrelated amyloid proteins such as Tau. In cellular models, JNR-LP2 mitigates hIAPP-induced cytotoxicity while exhibiting excellent intrinsic biocompatibility. Collectively, these findings identify JNRs as a modular and selective nanoplatform for amyloid inhibition, offering a novel precision-nanomedicine approach to T2DM.
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BibTeX
@article{jego2026janus,
title = {{Janus Polymeric Nanorods Inhibit human Amylin Oligomerization and Fibrillation for Potential Type 2 Diabetes Treatment}},
author = {Mathilde Jégo and Sandra Kalem and Irene Antignano and David Siefker and Mingsheng Ji and Julia Kaffy and Lynda Benrabah and Chloé Cayrou and Kawthar Bouchemal and Mélanie Hery and Erwan Nicol and Sandrine Pensec and Jutta Rieger and Claire Smadja and Sandrine Ongeri and Laurent Bouteiller and Olivier Colombani and Myriam Taverna},
journal = {Small Science},
year = {2026},
month = jul,
doi = {10.1002/smsc.70326},
url = {https://hal.sorbonne-universite.fr/hal-05772372v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Janus Polymeric Nanorods Inhibit human Amylin Oligomerization and Fibrillation for Potential Type 2 Diabetes Treatment
AU - Mathilde Jégo
AU - Sandra Kalem
AU - Irene Antignano
AU - David Siefker
AU - Mingsheng Ji
AU - Julia Kaffy
AU - Lynda Benrabah
AU - Chloé Cayrou
AU - Kawthar Bouchemal
AU - Mélanie Hery
AU - Erwan Nicol
AU - Sandrine Pensec
AU - Jutta Rieger
AU - Claire Smadja
AU - Sandrine Ongeri
AU - Laurent Bouteiller
AU - Olivier Colombani
AU - Myriam Taverna
PY - 2026
DA - 2026/07/27
JO - Small Science
DO - 10.1002/smsc.70326
UR - https://hal.sorbonne-universite.fr/hal-05772372v1
AB - Protein misfolding and aggregation of human islet amyloid polypeptide (hIAPP) are central to β-cell dysfunction in type 2 diabetes mellitus (T2DM). 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-affinity, sequence-specific interactions. These anisotropic poly(N, N-dimethylacrylamide) nanostructures, synthesized via reversible addition fragmentation chain transfer polymerization, self-assemble to display a β-hairpin mimetic ligand (LP2) on one face, enabling multivalent and directional binding. Biophysical assays reveal that JNR-LP2 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-LP2 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-target activity against unrelated amyloid proteins such as Tau. In cellular models, JNR-LP2 mitigates hIAPP-induced cytotoxicity while exhibiting excellent intrinsic biocompatibility. Collectively, these findings identify JNRs as a modular and selective nanoplatform for amyloid inhibition, offering a novel precision-nanomedicine approach to T2DM.
SN - 2688-4046
ER -