Oral glucose-responsive nanoparticles loaded with artemisinin induce pancreatic β-cell regeneration for the treatment of type 2 diabetes.

J Colloid Interface Sci

School of Life Science, South China Normal University, Guangzhou 510631 China; Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou 510631 China; South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research, Panyu Central Hospital, Guangzhou 511400 China. Electronic address:

Published: January 2025

Type 2 diabetes (T2D) is a chronic disease characterized by long-term insulin resistance (IR) and pancreatic β-cell dysfunction. Conventional T2D medication ignores pancreatic β-cell damage. In this study, we designed an oral glucose-responsive nanoparticle for pancreatic β-cell regeneration and treatment of T2D. It was formed by carboxymethyl chitosan (CMC) grafted with 3-aminophenylboronic acid (APBA) as the shell and small-molecule citrus pectin (MCP) spheres encapsulating artemisinin (Art) connected by borate ester bonds. The prepared CMC-APBA wrapped Art-loaded MCP nanoparticles (CAM@Art) had therapeutic effects for the treatment of IR, antioxidant and promotion of pancreatic α-cell differentiation in vitro experiments. In addition, in vivo experiments showed that CAM@Art could reduce blood glucose, oxidative stress and inflammation levels and reverse IR in diabetic rats. Importantly, pancreatic β-cell regeneration was found in islets in vivo. Mechanistically, CAM@Art promotes pancreatic α-cell differentiation by promoting overexpression of the transcription factor Pax4 and ectopic expression of Arx. The results suggest that the present study provides a promising therapeutic strategy for the treatment of diabetic pancreatic β-cell dysfunction.

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http://dx.doi.org/10.1016/j.jcis.2025.01.051DOI Listing

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