Synthesis of a Smart Gold Nano‐vehicle for Liver Specific Drug Delivery

Abstract

Abstract. Targeting drug formulations to specific tissues and releasing the bioactive content in response to a certain stimuli remains a significant challenge in the field of biomedical science. We have developed a nanovehicle that can be used to deliver "drugs" to "specific" tissues. For this, we have simultaneously modified the surface of the nanovehicle with "drugs" and "tissue-specific ligands". The "tissue-specific ligands" will target the nanovehicle to the correct tissue and release the "drug" of interest in response to specific stimuli. We have synthesised a "lactose surface-modified gold nanovehicle" to target liver cells and release the model fluorescent drug (coumarin derivative) in response to the differential glutathione concentration (between blood plasma and liver cells). Lactose is used as the liver-specific targeting ligand given the abundance of L-galactose receptors in hepatic cells. The coumarin derivative is used as a fluorescent tag as well as a linker for the attachment of various biologically relevant molecules. The model delivery system is compatible with a host of different ligands and hence could be used to target other tissues as well in future. The synthesised nanovehicle was found to be non-toxic to cultured human cell lines even at elevated non-physiological concentrations as high as 100 μg/mL. We discover that the synthesised gold-based nanovehicle shows considerable stability at low extracellular glutathione concentrations; however coumarin is selectively released at high hepatic glutathione concentration.

Intraorgan Targeting of Gold Conjugates for Precise Liver Cancer Treatment

“…Galactose-functionalized nanoparticles, especially GNPs, provide a promising strategy called cluster effect − for treating liver because the high density and multiantennary modification of galactose increased the dissociation constant ( K d value) of particles with ASGP-R. Herein, we propose that the biological specificity of drugs to treat hepatic carcinoma will not only rely on the ligands on the carriers for receptor recognition but also be determined by the performance of gold conjugates with designed structure. To prove our hypothesis, GNPs, PTX, and galactose (Gal) are employed as the model carrier, drug, and targeting ligand to fabricate ASGP-R-targeting PTX-conjugated GNPs for a precise treatment of liver cancer.…”

pH‐dependent immobilization of urease on glutathione‐capped gold nanoparticles

“…Our group has reported the use of nanoparticles in biomedical applications 37,38 and catalysis [39][40][41][42][43][44][45][46][47][48][49][50][51][52] in the past. Here we have demonstrated the use of gold nanoparticles for immobilization of urease, a technique that could potentially be used to immobilize other relevant proteins and bioactive peptides.…”

Small Molecule-Based Enzyme Inhibitors in the Treatment of Primary Hyperoxalurias

“…Nowadays, the development of smart nanocarrier-based drug delivery systems is at the focus of the pharmaceutical technology, and different nanocarriers have been designed and evaluated [ 174 ]. Specific bioencapsulation strategies to target hepatocytes have been developed [ 175 , 176 , 177 ], and the use of polymeric micelles is one of the most attractive alternatives [ 178 ]. Their core-shell architecture wherein the hydrophobic core plays the role of a natural carrier for hydrophobic drugs and the hydrophilic shell allows the stabilization of the nanoparticle in aqueous solutions.…”

“…In this field, our research group is making some efforts in terms of design and synthesis of chitosan-modified polymeric micelles for targeting hepatocytes [ 182 ]. For that, two hepatocyte cell features have been taken into account: (a) the high expression level on hepatocytes of asialoglycoprotein receptors (ASGPR) vs minimal expression on extrahepatic cells [ 175 , 183 ]; (b) the different concentration of glutathione (GSH) in blood plasma (10µM) vs hepatic cells (10 mM) [ 177 ]. Thus, different types of ligands are used to decorate the chitosan micelle: deoxycholic acid as a hydrophobic moiety [ 183 ], polyethylene glycol as a protective agent, avoiding micelle removal by the reticuloendothelial system [ 174 , 181 ], galactose derivative as a specific liver-targeting ligand [ 177 , 184 ], and cystamine as redox-triggered burst drug release moiety [ 185 ].…”