Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd₃N@C₈₀: A New Theranostic Agent for Combating Oxidative Stress and Resolving Inflammation

Abstract

Antioxidative and anti-inflammatory effects of trimetallic nitride endohedral fullerenes carboxyl-Gd3N@C80, a newly developed magnetic resonance imaging (MRI) contrast agent, were investigated. All hydrochalarone and carboxyl-functionalized fullerenes showed effective radical (hydroxyl and superoxide anion) scavenging, whereas the carboxyl-Gd3N@C80 more efficiently attenuated lipopolysaccharide (LPS) induced oxidative stress in macrophages. Carboxyl-Gd3N@C80 also suppressed LPS-elicited mRNA expression of pro-inflammatory inducible nitric oxide synthase and tumor necrosis factor-alpha, and upregulated antioxidative enzyme axis Nrf2 and heme oxygenase-1, possibly via ERK but not AKT signaling pathways. Therefore, carboxyl-Gd3N@C80 held a great promise in becoming a novel theranostic nanoplatform for simultaneously deliver MRI contrast and therapeutic functions to inflammation-related diseases.

C60-β-cyclodextrin conjugates for enhanced nucleus delivery of doxorubicin

“…22–25 Additionally, fullerenes or their derivatives can be used as a secondary drug. A notable example is their ability to scavenge reactive oxygen species (ROS), 26–31 thereby offering protection from side effects of chemotherapy drugs such as doxorubicin. 32,33…”

“…[22][23][24][25] Additionally, fullerenes or their derivatives can be used as a secondary drug. A notable example is their ability to scavenge reactive oxygen species (ROS), [26][27][28][29][30][31] thereby offering protection from side effects of chemotherapy drugs such as doxorubicin. 32,33 Compared to hydrophobic interactions, host-guest chemistry is a more well-defined supramolecular approach 34 provides protection from the environment, and selective loading/release for the drugs.…”

Regioselective Synthesis and Characterization of Tris- and Tetra-Prato Adducts of M3N@C80 (M = Y, Gd)

“…Chemical functionalization of trimetallic nitride template-endohedral metallofullerenes (TNT-EMFs or M 3 N@ I h -C 80 , denoted as M 3 N@C 80 ) have attracted considerable attention for the preparations of new functional materials such as photovoltaic devices and magnetic resonance imaging-contrast agents (MRI-CAs). − To obtain these materials, it is important to have suitable molecular designs. For instance, the fullerene derivatives with specific addition patterns often display better performance as solar cells by forming a specific orientation or packing of the molecules on the surface of devices .…”

A highly efficient hybrid peptide ameliorates intestinal inflammation and mucosal barrier damage by neutralizing lipopolysaccharides and antagonizing the lipopolysaccharide‐receptor interaction

“…[22][23][24][25] Furthermore, LPS induces several functional responses that contribute to inflammation and upregulates approximately 100 different genes, including those encoding pro-inflammatory cytokines, signaling molecules, and transcription regulators. 26,27 Excessive exposure to LPS results in a high rate of mortality and is the most common cause of death in intensive care units. 28,29 Traditionally, medications such as opioids, steroids, and nonsteroidal anti-inflammatory drugs have been commonly used for the treatment of inflammation.…”

“…Lipopolysaccharide (LPS), otherwise known as endotoxin, is a major constituent of the outer membrane of Gram‐negative bacillus, and its release is a potent inducer of intestinal inflammation and mucosal barrier damage 22‐25 . Furthermore, LPS induces several functional responses that contribute to inflammation and upregulates approximately 100 different genes, including those encoding pro‐inflammatory cytokines, signaling molecules, and transcription regulators 26,27 . Excessive exposure to LPS results in a high rate of mortality and is the most common cause of death in intensive care units 28,29 …”