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Peptide-functionalized nanocapsules for targeted inhibition of β2-microglobulin amyloid aggregation
Lin Tang1,2, Miao Sun3, Junnan Chen2
1Department of Medical Imaging, Qilu Medical University, 255100, P. R. China.
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.
Insights
A novel nanocomposite, NC-CF, effectively removes β2-microglobulin (β2m) and prevents its aggregation, offering a promising treatment for dialysis-related amyloidosis (DRA). This approach also protects cells from toxicity, suggesting potential therapeutic benefits.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Nephrology
Background:
- Dialysis-related amyloidosis (DRA) is a serious complication of long-term dialysis.
- It is caused by the accumulation of beta-2 microglobulin (β2m) amyloid fibrils.
- Removing β2m is a key strategy for managing DRA.
Purpose of the Study:
- To develop a β2m-binding peptide (CF)-functionalized nanocomposite (NC-CF).
- To evaluate NC-CF's efficacy in sequestering β2m and preventing its aggregation.
- To assess NC-CF's biocompatibility and cytoprotective effects.
Main Methods:
- Functionalization of protein nanocapsules with β2m-binding peptides (CF).
- Assessment of β2m aggregation modulation and adsorption capacity.
- Evaluation of biocompatibility and cytotoxicity mitigation using cell models.
Main Results:
- NC-CF effectively modulates β2m aggregation, forming larger clumps and preventing further fibril formation.
- NC-CF demonstrates a high adsorption capacity for β2m during simulated dialysis.
- NC-CF shows excellent biocompatibility and protects cells from β2m aggregate-induced toxicity (>70% protection rate).
Conclusions:
- NC-CF is a promising nanoinhibitor for β2m aggregation.
- NC-CF shows potential as an efficient adsorbent for β2m removal during dialysis.
- NC-CF may serve as a cytoprotective agent to alleviate DRA and its associated toxicity.
