A RAGE-antagonist peptide potentiates polymeric micelle-mediated intracellular delivery of plasmid DNA for acute lung injury gene therapy

Piao, Chunxian; Zhuang, Chuanyu; Choi, Myoungjee; Ha, Junkyu; Lee, Minhyung

doi:10.1039/d0nr01367f

Cited by 20 publications

(14 citation statements)

References 32 publications

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“…It has been reported that abnormal inflammatory factors are essential factors in the occurrence and development of ALI, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [3]. As such, removing the excessive production of those cytokines by anti-inflammatory agents, including corticosteroids, such as methylprednisolone [4], dexamethasone [5], prednisolone [6], represented a promising strategy to prevent and treat ALI [7]. However, most of these drugs have no beneficial effect on ALI patients because of their low efficacy and severe side effects.…”

Section: Introductionmentioning

confidence: 99%

Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis

Huang

Liu

et al. 2020

Aging

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Acute lung injury (ALI) is a critical clinical condition with a high mortality rate. It is believed that the inflammatory storm is a critical contributor to the occurrence of ALI. Fucoxanthin is a natural extract from marine seaweed with remarkable biological properties, including antioxidant, anti-tumor, and anti-obesity. However, the anti-inflammatory activity of Fucoxanthin has not been extensively studied. The current study aimed to elucidate the effects and the molecular mechanism of Fucoxanthin on lipopolysaccharide-induced acute lung injury. In this study, Fucoxanthin efficiently reduced the mRNA expression of pro-inflammatory factors, including IL-10, IL-6, iNOS, and Cox-2, and down-regulated the NF-κB signaling pathway in Raw264.7 macrophages. Furthermore, based on the network pharmacological analysis, our results showed that anti-inflammation signaling pathways were screened as fundamental action mechanisms of Fucoxanthin on ALI. Fucoxanthin also significantly ameliorated the inflammatory responses in LPS-induced ALI mice. Interestingly, our results revealed that Fucoxanthin prevented the expression of TLR4/MyD88 in Raw264.7 macrophages. We further validated Fucoxanthin binds to the TLR4 pocket using molecular docking simulations. Altogether, these results suggest that Fucoxanthin suppresses the TLR4/MyD88 signaling axis by targeting TLR4, which inhibits LPS-induced ALI, and fucoxanthin inhibition may provide a novel strategy for controlling the initiation and progression of ALI.

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Section: Introductionmentioning

confidence: 99%

Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis

Huang

Liu

et al. 2020

Aging

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“…Synthetic polymers are usually coated with polyethylene glycol (PEG) to reduce their toxicity and increase their solubility. Their high drug-loading capacity makes them favorable carriers for in vivo therapies; 102 they deliver drugs 19,23,[28][29][30]34,[70][71][72] and genes 31,33,53,[62][63][64][65][68][69][70][71][72][73] to the targeted site or act as therapeutic agents by themselves 52,67 for ALI treatment (Table 3).…”

Section: Polymeric Nanomedicinementioning

confidence: 99%

“…72 In a subsequent study, the RAGE-antagonist peptide (RAP) increased the gene delivery efficiency of PAM-D, and the RAP inhibited the RAGE-signal to show antiinflammatory effects. 69 Cholesterol-conjugated polyamidoamine micelles could deliver pHO-1 (heme-oxygenase -1 plasmid) along with RSV or Cur, in which pHO-1 induced HO-1 expression to decrease pro-inflammatory cytokines, and RSV or Cur inhibited the inflammatory reactions synergically. 70,71 The phosphorus dendrimers have been shown to have more efficiency in the cellular delivery of siRNA 108 and exhibited anti-inflammatory properties simultaneously.…”

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confidence: 99%

Nanomedicine-Based Therapeutics to Combat Acute Lung Injury

Bian¹,

Cai²,

Cui³

et al. 2021

IJN

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Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) may lead to a life-threatening form of respiratory failure, resulting in high mortality of up to 30-40% in most studies. Although there have been decades of research since ALI was first described in 1967, the clinical therapeutic alternatives for ALI are still in a state of limited availability. Supportive treatment and mechanical ventilation still have priority. Despite some preclinical studies demonstrating the benefit of pharmacological interventions, none of these has been proved completely effective to date. Recent advances in nanotechnology may shed new light on the pharmacotherapy of ALI. Nanomedicine possesses targeting and synergistic therapeutic capability, thus boosting pharmaceutical efficacy and mitigating the side effects. Currently, a variety of nanomedicine with diverse frameworks and functional groups have been elaborately developed, in accordance with their lung targeting ability and the pathophysiology of ALI. The in-depth review of the current literature reveals that liposomes, polymers, inorganic materials, cell membranes, platelets, and other nanomedicine approaches have conferred attractive therapeutic benefits for ALI treatment. In this review, we explore the recent progress in the study of the nanomedicinebased therapy of ALI, presenting various nanomedical approaches, drug choices, therapeutic strategies, and outcomes, thereby providing insight into the trends.

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“…The unique advantages of RNAi, including high efficiency, sequence specificity, and fewer side effects, have made it a promising modality for antiinflammation treatment by silencing the expression of inflammation-related genes [14][15][16][17]. Among them, the patternrecognition receptor for advanced glycation end product (RAGE) is an important mediator that regulates the pro-inflammatory and pro-apoptotic processes in the IR-injured myocardium by accumulating various ligands at the inflammation area [18][19][20]. Therefore, siRNA-mediated RNAi against RAGE in cardiomyocytes holds great potentials as a therapeutic paradigm for myocardial IR injury.…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury

et al. 2022

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Myocardial ischemia reperfusion (IR) injury is closely related to the overwhelming inflammation in the myocardium. Herein, cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species (ROS)-ultrasensitive co-delivery of dexamethasone (Dex) and RAGE small interfering RNA (siRAGE) to attenuate myocardial inflammation. PPTP, a ROS-degradable polycation based on PGE 2 -modified, PEGylated, ditellurium-crosslinked polyethylenimine (PEI) was developed to surface-decorate the Dex-encapsulated mesoporous silica nanoparticles (MSNs), which simultaneously condensed siRAGE and gated the MSNs to prevent the Dex pre-leakage. Upon intravenous injection to IR-injured rats, the nanotherapeutics could be efficiently transported into the inflamed cardiomyocytes via PGE 2 -assisted recognition of over-expressed E-series of prostaglandin (EP) receptors on the cell membranes. Intracellularly, the over-produced ROS degraded PPTP into small segments, promoting the release of siRAGE and Dex to mediate effective RAGE silencing (72%) and cooperative antiinflammatory effect. As a consequence, the nanotherapeutics notably suppressed the myocardial fibrosis and apoptosis, ultimately recovering the systolic function. Therefore, the current nanotherapeutics represent an effective example for the co-delivery and on-demand release of nucleic acid and chemodrug payloads, and might find promising utilities toward the synergistic management of myocardial inflammation. Electronic Supplementary Material Supplementary material (experimental methods, RNA and primer sequences, 1 H NMR spectra, FTIR spectrum, TEM images, zeta potential, drug loading content, RNA and drug release, cytotoxicity, etc.) is available in the online version of this article at 10.1007/s12274-022-4553-6.

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A RAGE-antagonist peptide potentiates polymeric micelle-mediated intracellular delivery of plasmid DNA for acute lung injury gene therapy

Abstract:
Pulmonary gene delivery system was developed based on RAGE-antagonist peptide and dexamethasone-conjugated polyamidoamine.

Cited by 20 publications

References 32 publications

Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis

Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis

Nanomedicine-Based Therapeutics to Combat Acute Lung Injury

Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury

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A RAGE-antagonist peptide potentiates polymeric micelle-mediated intracellular delivery of plasmid DNA for acute lung injury gene therapy

Abstract: Pulmonary gene delivery system was developed based on RAGE-antagonist peptide and dexamethasone-conjugated polyamidoamine.

Cited by 20 publications

References 32 publications

Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis

Fucoxanthin attenuates LPS-induced acute lung injury via inhibition of the TLR4/MyD88 signaling axis

Nanomedicine-Based Therapeutics to Combat Acute Lung Injury

Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury

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Product

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Abstract:
Pulmonary gene delivery system was developed based on RAGE-antagonist peptide and dexamethasone-conjugated polyamidoamine.