Arginine–glycine–aspartic acid–polyethylene glycol–polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture

Abstract

The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine–glycine–aspartic acid (RGD) peptide. Our studies demonstrate that RGD–polyethylene glycol (PEG)–PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT–MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system.

Keywords:

• dendrimer
• arginine–glycine–aspartic acid (RGD)
• liver cell
• spheroid culture
• ammonia metabolism

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Arginine–Glycine–Aspartic Acid–Polyethylene Glycol–Polyamidoamine Dendrimer Conjugate Improves Liver-Cell Aggregation and Function in 3-D Spheroid Culture [Corrigendum]

Acknowledgments

This work was supported by the Natural Science Foundation of Fujian Province (2013J01309), the National Natural Science Foundation of China (81470872), and the Construction Project of National Key Clinical Subject of General Surgery. The authors would like to thank Wen Wang from the College of Materials Science and Engineering, Fujian Normal University, for theory and technical support of the synthesis of the RGD-PEG-PAMAM conjugate.

Disclosure

The authors report no conflicts of interest in this work.