Abstract
Amyloid fibrils generally display chirality, a feature which has rarely been exploited in the development of therapeutics against amyloid diseases. This study reports, for the first time, the use of mesoscopic chiral silica nanoribbons against the in vivo amyloidogenesis of human islet amyloid polypeptide (IAPP), the peptide whose aggregation is implicated in type 2 diabetes. The thioflavin T assay and transmission electron microscopy show accelerated IAPP fibrillization through elimination of the nucleation phase and shortening of the elongation phase by the nanostructures. Coarse-grained simulations offer complementary molecular insights into the acceleration of amyloid aggregation through their nonspecific binding and directional seeding with the nanostructures. This accelerated IAPP fibrillization translates to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental, and behavioral assays. This study has implicated the potential of employing chiral nanotechnologies against the mesoscopic enantioselectivity of amyloid proteins and their associated diseases.
| Original language | English |
|---|---|
| Article number | 1802825 |
| Number of pages | 13 |
| Journal | Small |
| Volume | 14 |
| Issue number | 47 |
| DOIs | |
| Publication status | Published - 22 Nov 2018 |
Keywords
- amyloidogenesis
- chirality
- human IAPP
- silica nanoribbons
- toxicity
Cite this
}
Mitigating Human IAPP Amyloidogenesis In Vivo with Chiral Silica Nanoribbons. / Faridi, Ava; Sun, Yunxiang; Okazaki, Yutaka; Peng, Guotao ; Gao, Jie; Kakinen, Aleksandr; Faridi, Pouya; Zhao, Mei; Javed, Ibrahim; Purcell, Anthony W; Davis, Thomas P; Lin, Sijie; Oda, Reiko; Ding, Feng; Ke , Pu Chun .
In: Small, Vol. 14, No. 47, 1802825, 22.11.2018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Mitigating Human IAPP Amyloidogenesis In Vivo with Chiral Silica Nanoribbons
AU - Faridi, Ava
AU - Sun, Yunxiang
AU - Okazaki, Yutaka
AU - Peng, Guotao
AU - Gao, Jie
AU - Kakinen, Aleksandr
AU - Faridi, Pouya
AU - Zhao, Mei
AU - Javed, Ibrahim
AU - Purcell, Anthony W
AU - Davis, Thomas P
AU - Lin, Sijie
AU - Oda, Reiko
AU - Ding, Feng
AU - Ke , Pu Chun
PY - 2018/11/22
Y1 - 2018/11/22
N2 - Amyloid fibrils generally display chirality, a feature which has rarely been exploited in the development of therapeutics against amyloid diseases. This study reports, for the first time, the use of mesoscopic chiral silica nanoribbons against the in vivo amyloidogenesis of human islet amyloid polypeptide (IAPP), the peptide whose aggregation is implicated in type 2 diabetes. The thioflavin T assay and transmission electron microscopy show accelerated IAPP fibrillization through elimination of the nucleation phase and shortening of the elongation phase by the nanostructures. Coarse-grained simulations offer complementary molecular insights into the acceleration of amyloid aggregation through their nonspecific binding and directional seeding with the nanostructures. This accelerated IAPP fibrillization translates to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental, and behavioral assays. This study has implicated the potential of employing chiral nanotechnologies against the mesoscopic enantioselectivity of amyloid proteins and their associated diseases.
AB - Amyloid fibrils generally display chirality, a feature which has rarely been exploited in the development of therapeutics against amyloid diseases. This study reports, for the first time, the use of mesoscopic chiral silica nanoribbons against the in vivo amyloidogenesis of human islet amyloid polypeptide (IAPP), the peptide whose aggregation is implicated in type 2 diabetes. The thioflavin T assay and transmission electron microscopy show accelerated IAPP fibrillization through elimination of the nucleation phase and shortening of the elongation phase by the nanostructures. Coarse-grained simulations offer complementary molecular insights into the acceleration of amyloid aggregation through their nonspecific binding and directional seeding with the nanostructures. This accelerated IAPP fibrillization translates to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental, and behavioral assays. This study has implicated the potential of employing chiral nanotechnologies against the mesoscopic enantioselectivity of amyloid proteins and their associated diseases.
KW - amyloidogenesis
KW - chirality
KW - human IAPP
KW - silica nanoribbons
KW - toxicity
UR - http://www.scopus.com/inward/record.url?scp=85055693835&partnerID=8YFLogxK
U2 - 10.1002/smll.201802825
DO - 10.1002/smll.201802825
M3 - Article
VL - 14
JO - Small
JF - Small
SN - 1613-6810
IS - 47
M1 - 1802825
ER -