In Situ Nanoreactor for Photosynthesizing H₂ Gas To Mitigate Oxidative Stress in Tissue Inflammation

Abstract

Hydrogen gas can reduce cytotoxic reactive oxygen species (ROS) that are produced in inflamed tissues. Inspired by natural photosynthesis, this work proposes a multicomponent nanoreactor (NR) that comprises chlorophyll a, l-ascorbic acid, and gold nanoparticles that are encapsulated in a liposomal (Lip) system that can produce H gas in situ upon photon absorption to mitigate inflammatory responses. Unlike a bulk system that contains free reacting molecules, this Lip NR system provides an optimal reaction environment, facilitating rapid activation of the photosynthesis of H gas, locally providing a high therapeutic concentration thereof. The photodriven NR system reduces the degrees of overproduction of ROS and pro-inflammatory cytokines both in vitro in RAW264.7 cells and in vivo in mice with paw inflammation that is induced by lipopolysaccharide (LPS). Histological examinations of tissue sections confirm the ability of the NR system to reduce LPS-induced inflammation. Experimental results indicate that the Lip NR system that can photosynthesize H gas has great potential for mitigating oxidative stress in tissue inflammation.

An In Situ Depot for Continuous Evolution of Gaseous H2 Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis

“…[9] Thet herapeutic potential of Mg@PLGA MPs in mitigating the inflammatory responses of RAW264.7 cells stimulated by lipopolysaccharide (LPS) for 6h,a tw hich time the ROS level peaked, was investigated in vitro.T he groups that were treated with empty PLGA MPs or free Mg were used as controls.T he concentrations of empty PLGA MPs and free Mg that were used in the study were equivalent to those in Mg@PLGA MPs.T he production of ROS in LPS-stimulated RAW264.7 cells was qualitatively studied using acell-permeable fluorogenic probe of ROSa nd quantitatively measured using DCFH-DAdye. [5] Theexpressions of pro-inflammatory cytokines IL-1b,IL-6, and TNF-a in such cells were measured by enzyme-linked immunosorbent assay (ELISA), while double immunohistochemistry staining versus nucleus was carried out to visualize their intracellular intensities.P hotomicrographs were taken by confocal laser scanning microscopy (CLSM).…”

“…[4] Hydrogen (H 2 )i sc onsidered to be at herapeutic medical gas with anti-inflammatory effects. [5] In diseased cells,i t selectively reduces highly cytotoxic oxidative radicals,such as the hydroxyl radical and peroxynitrite;nevertheless,itaffects neither the metabolic oxidation-reduction reactions in normal cells nor disturbs the physiological ROSt hat participate in cell signaling. [6] H 2 is nontoxic even at high concentrations.…”

Polymer Dots Compartmentalized in Liposomes as a Photocatalyst for In Situ Hydrogen Therapy

“…However, the efficacy of these delivery strategies is restricted by the poor solubility of H 2 in water, saline, and blood. In 2017, ultrasound‐visible microbubbles of H 2 were developed to treat ischemia‐reperfusion injury and a multicomponent photocatalytic system comprising a photosensitizer and gold nanoparticles was designed to mitigate oxidative stress in tissue inflammation . However, there were a few drawbacks that seriously hindered their clinical application, including the high permeability of the microbubble membrane to H 2 and the low effectiveness of charge transfer from the photosensitizer to the gold nanoparticles …”

Gas‐Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy

“…Recently, a H 2 ‐delivery multicomponent nanoreactor was designed and constructed for local in situ H 2 generation with high therapeutic gas concentration only at the inflammatory site . This nanoreactor was made by a liposomal system containing chlorophyII a (Chl a ) as the photosensitizer, l ‐ascorbic acid as the electron donor, and gold nanoparticles as the catalyst ( Figure ).…”

“…Schematic illustration of the composition and structure of phototriggered nanoreactors for in situ photosynthesis of H 2 gas, and the further mitigation of the overproduction of oxidative stress by H 2 gas in LPS‐induced inflamed paw in a mouse model. Reproduced with permission . Copyright 2017, American Chemical Society.…”