Interplay between G protein-coupled receptors and nanotechnology

Jiang, Yuhong; Li, Yuke; Fu, Xiujuan; Wu, Yue; Wang, Rujing; Zhao, Mengnan; Mao, Canquan; Shi, Sanjun

doi:10.1016/j.actbio.2023.07.049

Cited by 5 publications

(3 citation statements)

References 139 publications

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“…94 In addition, nanoparticles as substrate support can capture a large number of target molecules or signal molecules. 90 Commonly used nanomaterials are: metal nanomaterials (AuNPs, Au-Ag metal nanoshells, 95 polypyrrole-gold nanoparticles composite nanostructure layer, 96 AgNPs, AgNP-TiP (hollow titanium phosphate ball), 97 nanocomposites of graphene and gold-palladium bimetallic nanoparticles 98 ); magnetic nanomaterials (fluorescent magnetic nanoparticles, [99][100][101] magnetic photonic crystals, 102 homogeneous FeCo nanoparticles with high magnetic moment 103 ); carbon nanomaterials (single-walled carbon nanotubes, 104 graphene, 105,106 GO, 107 boron nitride-gold nanoclusters composites 108 ); ABO 3 type perovskite oxide nanomaterial-LaFeO 3 109 ; TiO 2 mesocrystalline nanostructures 110 ;…”

Section: Advantages and Applications Of Nanostrategy In Cs Treatmentmentioning

confidence: 99%

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

Zheng,

Li,

et al. 2023

Medicinal Research Reviews

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As severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants continue to wreak havoc worldwide, the “Cytokine Storm” (CS, also known as the inflammatory storm) or Cytokine Release Syndrome has reemerged in the public consciousness. CS is a significant contributor to the deterioration of infected individuals. Therefore, CS control is of great significance for the treatment of critically ill patients and the reduction of mortality rates. With the occurrence of variants, concerns regarding the efficacy of vaccines and antiviral drugs with a broad spectrum have grown. We should make an effort to modernize treatment strategies to address the challenges posed by mutations. Thus, in addition to the requirement for additional clinical data to monitor the long‐term effects of vaccines and broad‐spectrum antiviral drugs, we can use CS as an entry point and therapeutic target to alleviate the severity of the disease in patients. To effectively combat the mutation, new technologies for neutralizing or controlling CS must be developed. In recent years, nanotechnology has been widely applied in the biomedical field, opening up a plethora of opportunities for CS. Here, we put forward the view of cytokine storm as a therapeutic target can be used to treat critically ill patients by expounding the relationship between coronavirus disease 2019 (COVID‐19) and CS and the mechanisms associated with CS. We pay special attention to the representative strategies of nanomaterials in current neutral and CS research, as well as their potential chemical design and principles. We hope that the nanostrategies described in this review provide attractive treatment options for severe and critical COVID‐19 caused by CS.

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Section: Advantages and Applications Of Nanostrategy In Cs Treatmentmentioning

confidence: 99%

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

Zheng,

Li,

et al. 2023

Medicinal Research Reviews

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“…Trypsin acts as the primary endogenous agonist of proteaseactivated receptor 2 (PAR2). 13 protein-coupled receptors (GPCRs) 14 that regulates intracellular signal transduction, including calcium, ERK, cAMP, and RhoA pathways. 15−17 PAR2 signaling is implicated in various cellular processes such as inflammation, angiogenesis, cell adhesion, proliferation, and migration, all of which are closely associated with tissue repair.…”

mentioning

confidence: 99%

“…Trypsin acts as the primary endogenous agonist of protease-activated receptor 2 (PAR2) . PAR2 is a subfamily of G protein-coupled receptors (GPCRs) that regulates intracellular signal transduction, including calcium, ERK, cAMP, and RhoA pathways. − PAR2 signaling is implicated in various cellular processes such as inflammation, angiogenesis, cell adhesion, proliferation, and migration, all of which are closely associated with tissue repair. , Cell migration at the leading edge comes first after wounding, followed by the displacement of cells in this region triggering orientated cell division of the cells. Increased proliferation can itself generate a surplus of migrating cells that later push the leading edge toward the wound center .…”

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confidence: 99%

Low-Dose Trypsin Accelerates Wound Healing via Protease-Activated Receptor 2

Xiang,

Jiang,

2023

ACS Pharmacol. Transl. Sci.

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The management of wounds remains a significant healthcare challenge, highlighting the need for effective wound healing strategies. To address this, it is crucial to explore the molecular mechanisms underlying tissue repair as well as explore potential therapeutic approaches. Trypsin, as a serine protease, has been clinically utilized for wound healing for decades; however, it still lacks systemic investigation on its role and related mechanism. This study aimed to investigate the effects of low-dose trypsin on wound healing both in vitro and in vivo. While trypsin is an endogenous stimulus for protease-activated receptor 2 (PAR2), we discovered that both low-dose trypsin and synthesized PAR2 agonists significantly enhanced the migration, adhesion, and proliferation of fibroblasts and macrophages, similar to the natural repair mechanism mediated by mast cell tryptase. Moreover, such cell functions induced by trypsin were largely inhibited by PAR2 blockade, indicating the participation of trypsin via PAR2 activation. Additionally, low-dose trypsin notably expedited healing and regeneration while enhancing collagen deposition in skin wounds in vivo. Importantly, upon stimulation of trypsin or PAR2 agonists, there were significant upregulations of genes including claudin-7 (Cldn7), occludin (Ocln), and interleukin-17A (IL-17A) associated with proliferation and migration, extracellular matrix (ECM), tight junction, and focal adhesion, which contributed to wound healing. In summary, our study suggested that a low-dose trypsin could be a promising strategy for wound healing, and its function was highly dependent on PAR2 activation.

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Dual‐functional Nanosized Albumin Facilitates CRISPR‐Cas9‐PAR2 to Mitigate Cytokine Storm via TLR4 and Pyroptosis Signaling

Li,

Zheng,

et al. 2024

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Protease‐activated receptor 2 (PAR2) widely modulates various cytokine secretions and inflammatory responses, while excessive cytokine releases and immune hyperactivation may trigger cytokine storm. However, the potential participation of PAR2 in cytokine storm remains elusive. CRISPR‐Cas9 as an efficient gene editing tool can be used for investigating the possible function of PAR2. In this study, albumin‐based nanoparticles (hAlbumin/cgPAR2) to protect and deliver CRISPR‐Cas9 for precise gene editing of PAR2 is constructed. Nanosized albumin largely assisted CRISPR‐Cas9‐PAR2 (cgPAR2) to enter cells via scavenger receptor‐mediated endocytosis, and then triggered potent transfection efficiency, consequently stimulating PAR2 knockout in vitro and in vivo. Apart from delivering CRISPR‐Cas9, nanosized albumin could be colocalized with TLR4 on endosome and promote PAR2 deficiency to attenuate TLR4/NF‐κB signaling, exerting the strong inhibitory effect of albumin in inflammatory responses depending on TLR4. Moreover, PAR2 deficiency induced by hAlbumin/cgPAR2 alleviated ERK/STING/NLRP3 signaling and GSDMD‐mediated pyroptosis, consequently inhibiting cytokine storm. Therefore, this study uncovered dual functions of nanosized albumin in delivering CRISPR‐Cas9 and facilitating PAR2 deficiency to prevent cytokine storm. It also uncovered that the significant role of PAR2 in modulating cytokine storm and provided a potential gene therapy strategy for treating this disease.

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Interplay between G protein-coupled receptors and nanotechnology

Cited by 5 publications

References 139 publications

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

Low-Dose Trypsin Accelerates Wound Healing via Protease-Activated Receptor 2

Dual‐functional Nanosized Albumin Facilitates CRISPR‐Cas9‐PAR2 to Mitigate Cytokine Storm via TLR4 and Pyroptosis Signaling

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