Synthesis of glycyrrhetinic acid-modified liposomes to deliver Murrayafoline A for treatment of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma is a common type of cancer associated with a high mortality rate. Among several bioactive compounds, Murrayafoline A (MuA) has been proved as a bio substance that exhibits great potentials in treating liver cancer. In order to overcome the high cytotoxicity and low solubility of MuA, a delivery system based on nanocarriers is necessary to deliver MuA towards the desired target. In the present study, 18β-glycyrrhetinic acid (GA), which is known as a ligand for liver targeting, was used to construct the cholesterol-poly (ethylene glycol)-glycyrrhetinic acid (GA-PEG-Chol) conjugate and liposome for MuA administration. The compound was then examined for therapeutic efficacy and safety in HUVEC and HepG2 cells in 2D and 3D cell cultures. Results have shown that MuA-loaded liposomes had IC50 value of 2 µM in HepG2 and had the cytosolic absorption of 8.83 ± 0.97 ng/105 cells, while The IC50 value of MuA-loaded liposomes in HUVEC cell lines was 15 µM and the the cytosolic absorption was recorded as 3.62 ± 0.61 cells. The drug test on the 3D cancer sphere platform of the HepG2 cancer sphere showed that MuA-loaded GA liposomes had the highest efficacy at a concentration of 100 µg/mL. In short, these results suggest that MuA-loaded GA liposomes have the potential for maintenance drug delivery and liver targeting.

Simple and Rapid Method of Microwell Array Fabrication for Drug Testing on 3D Cancer Spheroids

“…Figure B illustrates that as the laser power was increased from 40 to 100%, the tip of the microwells became sharper. This results can be explained based on the increased power, which can be associated with a greater amount of energy transferred to the PMMA surface, leading to the removal of larger material volumes and the generation of microchannels that are wider and deeper. ,,, However, in this study, due to the increasing speed parameter, the laser speed did not form the sharp tip of the microwell structure.…”

“…The exact shapes of the microwells and the relationship between laser speed and the depth of microwells are illustrated in Figure B. At higher engraving speeds, the engraving depth reduces as the laser beam spends less time at each point, resulting in less heat absorption by the material and a shallower and narrower microchannel. − …”

“…Living cells emit green fluorescence, which was detected by the excitation/emission 495/635 nm wavelength. Dead cells result in a bright red fluorescence with approximately 495/635 nm of excitation/emission from bonding with ethidium homodimer-I, which enters the cells through the broken membranes and attaches to nucleic acids . After washing twice with medium, samples were examined with an Olympus Fluorescence Microscope.…”

“…Dead cells result in a bright red fluorescence with approximately 495/635 nm of excitation/emission from bonding with ethidium homodimer-I, which enters the cells through the broken membranes and attaches to nucleic acids. 37 After washing twice with medium, samples were examined with an Olympus Fluorescence Microscope. The image of cell viability was taken and using the ImageJ software (Bethesda, Maryland, USA) to analyze the viability.…”

Simultaneous Activation of Immunogenic Cell Death and cGAS-STING Pathway by Liver- and Mitochondria-Targeted Gold(I) Complexes for Chemoimmunotherapy of Hepatocellular Carcinoma

“…This would enable their selective distribution to specific target organs, cells, or subcellular compartments, thereby minimizing exposure time to undesired proteins. 18β-glycyrrhetinic acid (GA), a ligand used for targeting the liver, can help modify drug delivery systems and improve the liver or hepatocyte drug uptake and efficacy. − Furthermore, incorporating mitochondrial-targeting scaffolds into TrxR inhibitors could facilitate the direct selective inhibition of mitochondrial TrxR. − Therefore, stabilizing the central gold atom with more stable ligands and enhancing the targeting ability of gold compounds could be an appropriate structural design strategy to overcome the drawbacks of gold complexes.…”