Back to Search
Start Over
A glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy.
- 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.)
- Subjects :
- Animals
Male
Blood Glucose drug effects
Blood Glucose analysis
Mice, Inbred C57BL
Diabetes Mellitus, Type 2 drug therapy
Mice
Diabetes Mellitus, Experimental drug therapy
Kidney metabolism
Kidney drug effects
Boronic Acids chemistry
Boronic Acids administration & dosage
Diabetic Nephropathies drug therapy
Reactive Oxygen Species metabolism
Polymers chemistry
Polymers administration & dosage
Subjects
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