Engineering of Exosomes to Target Cancer Metastasis

Zhang, Zhenjiang; Dombroski, Jenna A.; King, Michael R.

doi:10.1007/s12195-019-00607-x

Cited by 62 publications

(79 citation statements)

References 140 publications

(243 reference statements)

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“…Although not shown in ALS so far, exosomes can be engineered to deliver therapeutic molecules of choice. Other studies have shown that indeed exosome content can be modified to deliver cargo to recipient cells [ 168 ]. This aspect of exosome biology holds a great potential as exosomes can cross the blood–brain barrier [ 169 ] and deliver a molecule of choice to the central nervous system.…”

Section: Evs In Neurodegenerative Diseases—an Example Of Alsmentioning

confidence: 99%

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

Anđjus

Kosanović

Milićević

et al. 2020

IJMS

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Extracellular vesicles (EVs) have recently attracted a great deal of interest as they may represent a new biosignaling paradigm. According to the mode of biogenesis, size and composition, two broad categories of EVs have been described, exosomes and microvesicles. EVs have been shown to carry cargoes of signaling proteins, RNA species, DNA and lipids. Once released, their content is selectively taken up by near or distant target cells, influencing their behavior. Exosomes are involved in cell–cell communication in a wide range of embryonic developmental processes and in fetal–maternal communication. In the present review, an outline of the role of EVs in neural development, regeneration and diseases is presented. EVs can act as regulators of normal homeostasis, but they can also promote either neuroinflammation/degeneration or tissue repair in pathological conditions, depending on their content. Since EV molecular cargo constitutes a representation of the origin cell status, EVs can be exploited in the diagnosis of several diseases. Due to their capability to cross the blood–brain barrier (BBB), EVs not only have been suggested for the diagnosis of central nervous system disorders by means of minimally invasive procedures, i.e., “liquid biopsies”, but they are also considered attractive tools for targeted drug delivery across the BBB. From the therapeutic perspective, mesenchymal stem cells (MSCs) represent one of the most promising sources of EVs. In particular, the neuroprotective properties of MSCs derived from the dental pulp are here discussed.

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Section: Evs In Neurodegenerative Diseases—an Example Of Alsmentioning

confidence: 99%

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

Anđjus

Kosanović

Milićević

et al. 2020

IJMS

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“…During the past decade, many efforts have been devoted to transfect sEV-producing cells with plasmids encoding protein sequences that, once uploaded in the nanovesicles, are able to alter the phenotype of target cells [ 135 , 136 , 137 , 138 ]. However, a method to target M2 macrophages with sEVs capable of inducing their reprogramming to M1 anti-tumor phenotype is not yet available.…”

Section: Molecular Basis Of Tam Re-programming By Engineered Sevsmentioning

confidence: 99%

Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting

Fiani

Barreca

Sargiacomo

et al. 2020

IJMS

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Immunosuppression at tumor microenvironment (TME) is one of the major obstacles to be overcome for an effective therapeutic intervention against solid tumors. Tumor-associated macrophages (TAMs) comprise a sub-population that plays multiple pro-tumoral roles in tumor development including general immunosuppression, which can be identified in terms of high expression of mannose receptor (MR or CD206). Immunosuppressive TAMs, like other macrophage sub-populations, display functional plasticity that allows them to be re-programmed to inflammatory macrophages. In order to mitigate immunosuppression at the TME, several efforts are ongoing to effectively re-educate pro-tumoral TAMs. Extracellular vesicles (EVs), released by both normal and tumor cells types, are emerging as key mediators of the cell to cell communication and have been shown to have a role in the modulation of immune responses in the TME. Recent studies demonstrated the enrichment of high mannose glycans on the surface of small EVs (sEVs), a subtype of EVs of endosomal origin of 30–150 nm in diameter. This characteristic renders sEVs an ideal tool for the delivery of therapeutic molecules into MR/CD206-expressing TAMs. In this review, we report the most recent literature data highlighting the critical role of TAMs in tumor development, as well as the experimental evidences that has emerged from the biochemical characterization of sEV membranes. In addition, we propose an original way to target immunosuppressive TAMs at the TME by endogenously engineered sEVs for a new therapeutic approach against solid tumors.

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“…Our hypothesis can be tested in laboratories with the right and ability to conduct inexpensive and short-term tests proposed by cc-miRNAs as a means of combating COVID-19, SARS-CoV, and MERS-CoV coronaviruses. Since the size of cc-miRNAs is approximately 9 nm, they can be delivered via circulation to many organs as part of ordinary exosomes in human blood measuring 30-150 nm [11,12,13]. As part of exosomes, cc-miRNAs can be introduced into the lung by inhalation.…”

Section: Synthesis and Delivery Of Cc-mirnas Into Humansmentioning

confidence: 99%

The miRNA COMPLEXES AGAINST CORONAVIRUSES COVID-19, SARS-CoV, and MERS-CoV

Ivashchenko

Rakhmetullina

Akimniyazova

et al. 2020

Preprint

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The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses COVID-19, SARS-CoV, and MERS-CoV has been shown. Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of COVID-19, SARS-CoV, and MERS-CoV genomes. For complexes of seven cc-miRc for COVID-19, seven cc-miRs for SARS-CoV, and eight cc-miRm for MERS-CoV, the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

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Engineering of Exosomes to Target Cancer Metastasis

Cited by 62 publications

References 140 publications

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage

Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting

The miRNA COMPLEXES AGAINST CORONAVIRUSES COVID-19, SARS-CoV, and MERS-CoV

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