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A glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy.

Authors :
Zhang J
Wu T
Li C
Du J
Source :
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Aug; Vol. 372, pp. 347-361. Date of Electronic Publication: 2024 Jun 25.
Publication Year :
2024

Abstract

Diabetic nephropathy is a severe complication of diabetes. Treatment of diabetic nephropathy is an important challenge due to persistent hyperglycemia and elevated levels of reactive oxygen species (ROS) in the kidney. Herein, we designed a glycopolymersome that can treat type 2 diabetic nephropathy by effectively inhibiting hyperglycemia and ROS-associated diabetic nephropathy pathogenesis. The glycopolymersome is self-assembled from phenylboronic acid derivative-containing copolymer, poly(ethylene oxide) <subscript>45</subscript> -block-poly[(aspartic acid) <subscript>13</subscript> -stat-glucosamine <subscript>24</subscript> -stat-(phenylboronic acid) <subscript>18</subscript> -stat-(phenylboronic acid pinacol ester) <subscript>3</subscript> ] [PEO <subscript>45</subscript> -b-P(Asp <subscript>13</subscript> -stat-GA <subscript>24</subscript> -stat-PBA <subscript>18</subscript> -stat-PAPE <subscript>3</subscript> )]. PBA segment can reversibly bind blood glucose or GA segment for long-term regulation of blood glucose levels; PAPE segment can scavenge excessive ROS for renoprotection. In vitro studies confirmed that the glycopolymersomes exhibit efficient blood glucose responsiveness within 2 h and satisfactory ROS-scavenging ability with 500 μM H <subscript>2</subscript> O <subscript>2</subscript> . Moreover, the glycopolymersomes display long-acting regulation of blood glucose levels in type 2 diabetic nephropathy mice within 32 h. Dihydroethidium staining revealed that these glycopolymersomes reduced ROS to normal levels in the kidney, which led to 61.7% and 76.6% reduction in creatinine and urea levels, respectively, along with suppressing renal apoptosis, collagen accumulation, and glycogen deposition in type 2 diabetic nephropathy mice. Notably, the polypeptide-based glycopolymersome was synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs), thereby exhibiting favorable biodegradability. Overall, we proposed a new glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy, which could be extended to encompass the design of various multifunctional nanoparticles targeting diabetes and its associated complications.<br />Competing Interests: Declaration of competing interest The authors declare no conflict of interest.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1873-4995
Volume :
372
Database :
MEDLINE
Journal :
Journal of controlled release : official journal of the Controlled Release Society
Publication Type :
Academic Journal
Accession number :
38908757
Full Text :
https://doi.org/10.1016/j.jconrel.2024.06.049