Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages

Molinaro, Roberto; Pastò, Anna; Corbo, Claudia; Taraballi, Francesca; Giordano, Federica; Martinez, Jonathan O.; Zhao, Picheng; Wang, Xin; Zinger, Assaf; Boada, Christian; Hartman, Kelly A.; Tasciotti, Ennio

doi:10.1039/c9nr04253a

Cited by 53 publications

(44 citation statements)

References 26 publications

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“…Leukocytes represent an almost ideal source since they are circulating cells, have still "self " proteins, but they also normally adhere to inflamed blood vessels, extravasate in the surrounding tissue, and interact with foreign bodies. Thus, the use of leukocytes can provide active targeting for inflammation, making the use of such coating highly valuable for a wide array of applications that range from tumors to chronic inflammatory states such as sepsis IBDs (Molinaro et al, 2016(Molinaro et al, , 2019Corbo et al, 2017a;Martinez et al, 2018).…”

Section: Cell Membrane Coatingmentioning

confidence: 99%

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Rampado

Crotti

Caliceti

et al. 2020

Front. Bioeng. Biotechnol.

234

166

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In the last decades, the staggering progress in nanotechnology brought around a wide and heterogeneous range of nanoparticle-based platforms for the diagnosis and treatment of many diseases. Most of these systems are designed to be administered intravenously. This administration route allows the nanoparticles (NPs) to widely distribute in the body and reach deep organs without invasive techniques. When these nanovectors encounter the biological environment of systemic circulation, a dynamic interplay occurs between the circulating proteins and the NPs, themselves. The set of proteins that bind to the NP surface is referred to as the protein corona (PC). PC has a critical role in making the particles easily recognized by the innate immune system, causing their quick clearance by phagocytic cells located in organs such as the lungs, liver, and spleen. For the same reason, PC defines the immunogenicity of NPs by priming the immune response to them and, ultimately, their immunological toxicity. Furthermore, the protein corona can cause the physical destabilization and agglomeration of particles. These problems induced to consider the PC only as a biological barrier to overcome in order to achieve efficient NP-based targeting. This review will discuss the latest advances in the characterization of PC, development of stealthy NP formulations, as well as the manipulation and employment of PC as an alternative resource for prolonging NP half-life, as well as its use in diagnostic applications.

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Section: Cell Membrane Coatingmentioning

confidence: 99%

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Rampado

Crotti

Caliceti

et al. 2020

Front. Bioeng. Biotechnol.

234

166

View full text Add to dashboard Cite

show abstract

“…Many types of membranes have been used to fabricate membrane-camouflaged nanoparticles, including membranes from red blood cells, platelets, white blood cells, cancer cells and bacteria [10,11,12,13,14,15]. Meanwhile, incorporation of membrane proteins within the bilayer of biomimetic nanovesicles using a microfluidic-based platform offers a one-step solution to endow nanoparticles with multiple biological feature such as evading the mononuclear phagocytic system, crossing the biological barriers or targeting inflamed tissues [16,17,18]. However, without exception, fabrication of core–shell nanoparticles has required extraction of plasma membrane materials by cell lysis and membrane purification, a process that greatly increases the risk of contamination and destruction of functional surface proteins.…”

Section: Introductionmentioning

confidence: 99%

Cocktail Strategy Based on NK Cell-Derived Exosomes and Their Biomimetic Nanoparticles for Dual Tumor Therapy

Wang

Chen

et al. 2019

Cancers

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Successful cancer therapy requires drugs being precisely delivered to tumors. Nanosized drugs have attracted considerable recent attention, but their toxicity and high immunogenicity are important obstacles hampering their clinical translation. Here we report a novel “cocktail therapy” strategy based on excess natural killer cell-derived exosomes (NKEXOs) in combination with their biomimetic core–shell nanoparticles (NNs) for tumor-targeted therapy. The NNs were self- assembled with a dendrimer core loading therapeutic miRNA and a hydrophilic NKEXOs shell. Their successful fabrication was confirmed by transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). The resulting NN/NKEXO cocktail showed highly efficient targeting and therapeutic miRNA delivery to neuroblastoma cells in vivo, as demonstrated by two-photon excited scanning fluorescence imaging (TPEFI) and with an IVIS Spectrum in vivo imaging system (IVIS), leading to dual inhibition of tumor growth. With unique biocompatibility, we propose this NN/NKEXO cocktail as a new avenue for tumor therapy, with potential prospects for clinical applications.

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“…Some miRNAs have been shown to be abnormally expressed in sepsis, and changes in their expression may influence the pathology and progression of sepsis [14, 15, 16]. As, sepsis is a serious systemic inflammatory response syndrome [1, 2], our data indicated that miR-181a-5p is a potential therapeutic target for anti-inflammatory treatment [40, 41] of sepsis. However, this was just a preliminary study of miR-181a-5p in sepsis.…”

Section: Discussionmentioning

confidence: 77%

MicroRNA-181a-5p regulates inflammatory response of macrophages in sepsis

Huang

2019

Open Medicine

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AbstractThe aim of this study was to evaluate the role of miR-181a-5p in sepsis, and to further explore the molecular mechanism. RAW 264.7 cells were stimulated with 1 μg/ml LPS for 4 hours. Firstly, qRT-PCR and ELISA was adopted to evaluate the expression of miR-181a-5p and p ro-inflammatory cytokines in RAW 264.7 macrophages a fter LPS stimulation. Results showed that pro-inflammatory cytokines and miR-181a-5p were significantly increased after LPS treatment. Then, we identified that sirtuin-1 (SIRT1) was a direct target of miR-181a-5p and it was down-regulated in LPS treated RAW264.7 macrophages. Furthermore, the data suggested that the miR-181a-5p inhibitor significantly inhibited LPS enhanced inflammatory cytokines expression and NF-κB pathway activation, and these changes were eliminated by SIRT1 silencing. Moreover, the role of the miR-181a-5p inhibitor on sepsis was studied in vivo. We found that the miR-181a-5p inhibitor significantly decreased the secretion of inflammatory factors, and the levels of creatine (Cr), blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a serum for mice with sepsis. However, all the effects were reversed by SIRT1-siRNA. In summary, these results indicated that miR-181a-5p was involved in sepsis through regulating the inflammatory response by targeting SIRT1, suggesting that miR-181a-5p may be a potential target for the treatment of sepsis.

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Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages

Abstract: Here, we have demonstrated that biomimetic nanovesicles assembled from macrophages' membrane proteins are similar to macrophage-derived exosomes. The anti-inflammatory activity observed in vivo derives from their direct interaction with macrophages.

Cited by 53 publications

References 26 publications

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

Cocktail Strategy Based on NK Cell-Derived Exosomes and Their Biomimetic Nanoparticles for Dual Tumor Therapy

MicroRNA-181a-5p regulates inflammatory response of macrophages in sepsis

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