In Vivo Mitigation of Amyloidogenesis through Functional-Pathogenic Double-Protein Coronae

Amyloid diseases are global epidemics with no cure available. Herein, we report a first demonstration of in vivo mitigation of amyloidogenesis using biomimetic nano technology. Specifically, the amyloid fragments (b(a)) of beta-lactoglobulin, a whey protein, were deposited onto the surfaces of carbon nanotubes (b(a)CNT), which subsequently sequestered human islet amyloid polypeptide (IAPP) through functional-pathogenic double-protein coronae. Conformational changes at the b(a)-IAPP interface were studied by Fourier transform infrared, circular dichroism, and X-ray scattering spectroscopies. b(a)CNT eliminated the toxic IAPP species from zebrafish embryos, as evidenced by the assays of embryonic development, cell morphology, hatching, and survival as well as suppression of oxidative stress. In addition to IAPP, b(a)CNT also displayed high potency against the toxicity of amyloid-beta, thereby demonstrating the broad applicability of this biomimetic nanotechnology and the use of an embryonic zebrafish model for the high-throughput screening of a range of amyloidogenesis and their inhibitors in vivo.