Design of Nanohydrogels for Targeted Intracellular Drug Transport to the Trans-Golgi Network

Title data

Keller, Thorsten ; Trinks, Nora ; Brand, Jessica ; Trippmacher, Steffen ; Stahlhut, Philipp ; Albrecht, Krystina ; Papastavrou, Georg ; Koepsell, Hermann ; Sauer, Markus ; Groll, Jürgen:
Design of Nanohydrogels for Targeted Intracellular Drug Transport to the Trans-Golgi Network.
In: Advanced Healthcare Materials. Vol. 12 (2023) Issue 13 . - 2201794.
ISSN 2192-2659
DOI: https://doi.org/10.1002/adhm.202201794

Official URL:

Abstract in another language

Nanohydrogels combine advantages of hydrogels and nanoparticles. In particular, they represent promising drug delivery systems. Nanogel synthesis by oxidative condensation of polyglycidol prepolymers, that are modified with thiol groups, results in crosslinking by disulfide bonds. Hereby, biomolecules like the antidiabetic peptide RS1-reg, derived from the regulatory protein RS1 of the Na+-D-glucose cotransporter SGLT1, can be covalently bound by cysteine residues to the nanogel in a hydrophilic, stabilizing environment. After oral uptake, the acid-stable nanogels protect their loading during gastric passage from proteolytic degradation. Under alkaline conditions in small intestine the nanohydrogels become mucoadhesive, pass the intestinal mucosa and are taken up into small intestinal enterocytes by endocytosis. Using Caco-2 cells as a model for small intestinal enterocytes, by confocal laser scanning microscopy and structured illumination microscopy, the colocalization of fluorescent-labeled RS1-reg with markers of endosomes, lysosomes, and trans-Golgi-network after uptake with polyglycidol-based nanogels formed by precipitation polymerization is demonstrated. This indicates that RS1-reg follows the endosomal pathway. In the following, the design of bespoken nanohydrogels for specific targeting of RS1-reg to its site of action at the trans-Golgi network is described that might also represent a way of targeted transport for other drugs to their targets at the Golgi apparatus.

Further data

Item Type:	Article in a journal
Refereed:	Yes
Keywords:	drug delivery; nanohydrogels; regulation of the Na+-D-glucose cotransporter SGLT1 in intestine; regulatory protein RS1; targeted transport
Institutions of the University:	Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Physical Chemistry II Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Physical Chemistry II > Chair Physical Chemistry II - Univ.-Prof. Dr. Georg Papastavrou
Result of work at the UBT:	Yes
DDC Subjects:	500 Science 500 Science > 540 Chemistry
Date Deposited:	22 May 2023 06:26
Last Modified:	22 May 2023 07:30
URI:	https://eref.uni-bayreuth.de/id/eprint/76487