Exploring the Curvature-Dependence of Boron Nitride Nanoparticles on the Inhibition of hIAPP Aggregation

Nanoparticles, particularly carbon nanoparticles, have gathered significant interest in the field of anti-aggregation research. However, due to their cytotoxicity, the exploration of biocompatible nanoparticles has become a new frontier in the quest for drugs against human amyloid diseases. The application of non-cytotoxic and biocompatible boron nitride (BN) nanoparticles against amyloid aggregation has been probed to tackle this issue. BN nanoparticles displayed inhibitory activity against the aggregation of Aβ and α-syn peptides. In this work, the effect of BN nanoparticles on the dimerization of hIAPP, which is associated with the pathogenesis of type 2 diabetes, is studied. BN nanoparticles prevent the misfolding of hIAPP into β-sheet-rich aggregates. On varying the curvature, the nanoparticles display variation in the interaction preference with hIAPP. Interestingly, as the hydrophobicity of the nanoparticles increases from (5,5) BN nanotube to BN nanosheet, the interaction propensity shifts from N-terminal to the amyloid prone C-terminal of hIAPP. The hydrophobic and aromatic stacking interactions are a contributing factor toward the binding between hIAPP and BN. Due to this, the flat surface of the nanosheet shows better interaction potential toward hIAPP, compared to the nanotubes. Further, the nanoparticles can also disassemble preformed hIAPP fibrils, and the effect is more pronounced for (5,5) nanotube and the nanosheet. This study provides insight into the inhibitory mechanism of hIAPP aggregation by boron nitride nanoparticles and also an understanding of the significance of the curvature of nanoparticles in their interaction with amyloid peptides, which is valuable for the design of antiamyloid drugs.