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

Abstract

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.

Determination of Aminophylline in Human Serum Using Hydrogel Microspheres for Coupled Surface-Enhanced Raman Spectroscopy (SERS) and Solid-Phase Extraction

“…Microgels are hydrogels of a few hundred to a thousand nanometers in size, which are three-dimensional (3D) polymer networks cross-linked by chemical bonds or physical interactions, which are fully affinity with solvents and swell but insoluble. 13 Due to their small particle size, large specific surface area, and good biocompatibility, microgels have shown promising applications in many fields such as drug delivery and controlled release, [14][15][16] microreactors, 17 medical diagnostics, and biosensors. 18 The use of microgels as carriers for NMNPs allows them to be uniformly dispersed within the 3D network, thus effectively avoiding agglomeration of NMNPs.…”

Bimetallic DNAsome Decorated with G4‐DNA as a Nanozyme for Targeted and Enhanced Chemo/Chemodynamic Cancer Therapy

“…Chemodynamic therapy (CDT) has recently been emerged as one of the efficient noninvasive strategies for the treatment to their unique structural features such as unparallel biocompatibility, metal ion binding affinity and sequence specific duplex formation. [10][11][12][13][14] By exploring their metal ion binding affinity, various DNA-metal CDT agents have been reported. [15][16][17][18][19][20] Among them, Cu 2+ -based systems outperform over other metal ions owing to their excellent catalytic activity even in weakly acidic conditions.…”