Innovate efficient artificial antioxidants for stem cell therapy


April 05, 2023

(Nanowerk Highlights) The rapid development of regenerative medicine based on stem cell transplantation offers a promising treatment option for severe tissue injuries, such as heart function improvement, nerve cell regeneration, and refractory bone defects. However, an abnormal increase in reactive oxygen species (ROS) in injured tissue can severely impair stem cell proliferation, limiting the clinical applicability of stem cell transplantation.

ROS are molecules that can cause oxidative stress, causing cell damage and dysfunction, while antioxidants are enzymes that counteract the harmful effects of ROS by scavenging and neutralizing them.

Current methods for combating ROS involve the use of endogenous antioxidant molecules and antioxidant enzymes. However, this traditional antioxidant has limitations in clinical trials due to poor treatment efficiency. Antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) have been studied for their specificity and high efficiency in scavenging ROS, but their intrinsic drawback limits their potential applications. Consequently, there is an urgent need for artificial antioxidases with efficient ROS scavenging activity to address the increasing interest in anti-ROS materials.

Inspired by the coordination structure of Mn-based antioxidase (Mn-SOD), Professor Chong Cheng and Professor Ling Ye of Sichuan University have designed a new manganese coordinated polyphthalocyanine (Mn-PcBC) based biocatalyst as an artificial antioxidant to enhance stem cells. transplant results. Design and construction of a manganese-coordinated polyphthalocyanine-based biocatalyst Figure 1. Design and construction of Mn-PcBC. (Image courtesy of the researchers)

This biocatalyst displays axial Mn-N5 2D d-π-conjugated sites and networks, which function as artificial antioxidants to save the fate of stem cells. The researchers systematically explored the chemical structure, catalytic activity and catalytic mechanism of Mn-PcBC using experimental studies and theoretical calculations. Performance of ROS scavenging from manganese-coordinated polyphthalocyanine-based biocatalysts Figure 2. ROS scavenging performance from Mn-PcBC. (Image courtesy of the researchers)

They presented their findings in International Applied Chemistry (Manganese-Based Antioxidase Inspired Biocatalyst with Axial Mn-N5 2D d-π Conjugated Sites and Networks to Save the Fate of Stem Cells”).

The researchers synthesized Mn-PcBC using a unique coordination structure inspired by Mn-based antioxidants. Density functional theory (DFT) calculations reveal that the excellent catalytic activity of Mn-PcBC is associated with 2D and axial Mn-N-conjugated d-π networks5 coordination. Protection and differentiation performance of stem cells in high-level ROS microenvironments Figure 3. Stem cell differentiation and protection performance in high ROS microenvironment. (Image courtesy of the researchers)

In addition, this study demonstrated that Mn-PcBC can effectively protect mesenchymal stem cells in a high ROS-containing microenvironment, leading to increased survival rate, cytoskeleton organization, adhesion formation, and osteogenic differentiation.

Cheng and Ye report that, due to the structural benefits of polyphthalocyanine-based 2D networks and axial coordination, Mn-PcBC exhibits superior, versatile, and robust ROS-scavenging capabilities, such as H2HI2 and •O2far outperforming the previously reported Mn-based artificial antioxidants.

They concluded that the Mn-PcBC biocatalyst offers an efficient, multifaceted and potent artificial antioxidant for broad-spectrum ROS scavenging and has the potential to enhance stem cell-related therapies and address various ROS-mediated diseases. By
Michael is the author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: A Small FutureAnd
Nanoengineering: Skills and Tools for Making Technology Invisible
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