Peptide-functionalized nanocapsules for targeted inhibition of β2-microglobulin amyloid aggregation†

Abstract

Dialysis-related amyloidosis (DRA) is a severe complication in patients undergoing long-term dialysis, primarily driven by the deposition of β2-microglobulin (β2m) amyloid fibrils. The effective sequestration and removal of β2m from the bloodstream represent key therapeutic strategies for managing DRA. In this study, we developed a β2m-binding peptide (KDWSFYILAHTEF, denoted as CF)-functionalized nanocomposite (NC-CF), consisting of a protein nanocapsule surface modified with CF peptides to enable specific β2m binding. NC-CF effectively modulates β2m aggregation, transforming slender fibrils into larger clumps while providing steric hindrance to prevent further aggregation. With a high adsorption capacity, 1 μg of NC-CF can adsorb approximately 1 μg of β2m during dialysis, highlighting its potential as an efficient adsorbent for in vitro β2m removal. Furthermore, NC-CF exhibits excellent biocompatibility and significantly mitigates β2m aggregate-induced cytotoxicity, achieving a cell protection rate exceeding 70%. These findings suggest that NC-CF holds great promise as a cytoprotective agent and a nanoinhibitor of β2m aggregation in vivo. Overall, NC-CF offers a novel and effective approach for alleviating DRA by simultaneously removing β2m and safeguarding cells against amyloid-induced toxicity.