Exosomes as Immunotheranostic Nanoparticles

Natasha, G; Gundogan, Buket; Tan, Aaron; Farhatnia, Yasmin; Wu, Woffles; Rajadas, Jayakumar; Seifalian, Alexander M.

doi:10.1016/j.clinthera.2014.04.019

Cited by 89 publications

(69 citation statements)

References 54 publications

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“…They are also involved in transferring genetic materials, and modulation of immune response. Evidence indicates that they can be used as not only therapeutic agents targeted against disease but also diagnostic biomarkers for pathologic conditions [79]. Actually, NP-induced exosomes are signaling mediators, which provoke the activation of T helper cell type 1 and inflammatory responses [80].…”

Section: Extracellular Matrixmentioning

confidence: 99%

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

et al. 2017

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Extracellular matrix (ECM) is an extraordinarily complex and unique meshwork composed of structural proteins and glycosaminoglycans. The ECM provides essential physical scaffolding for the cellular constituents, as well as contributes to crucial biochemical signaling. Importantly, ECM is an indispensable part of all biological barriers and substantially modulates the interchange of the nanotechnology products through these barriers. The interactions of the ECM with nanoparticles (NPs) depend on the morphological characteristics of intercellular matrix and on the physical characteristics of the NPs and may be either deleterious or beneficial. Importantly, an altered expression of ECM molecules ultimately affects all biological processes including inflammation. This review critically discusses the specific behavior of NPs that are within the ECM domain, and passing through the biological barriers. Furthermore, regenerative and toxicological aspects of nanomaterials are debated in terms of the immune cells-NPs interactions.

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Section: Extracellular Matrixmentioning

confidence: 99%

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

et al. 2017

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“…Exosomes are uniquely suited for drug or gene delivery because they are naturally biocompatible, stable while circulating in the blood, and capable of crossing the blood brain barrier [ 113 ]. Dendritic cell-derived exosomes (dexosomes) have been successfully engineered to target helper T cells to stimulate cytotoxic T cell proliferation, influence T cell differentiation, and create an anti-tumor environment [ 114 ].…”

Section: Applications Of Exosomes To Cancer Diagnostics and Therapymentioning

confidence: 99%

“…Likewise, dexosomes generated only grade 1–2 adverse effects and were able to stabilize disease during a phase I clinical trial for non-small cell lung cancer patients [ 117 ]. Reviews have been recently published for exosomes as cancer vaccines [ 113 ] and dexosome immunotherapy [ 118 ].…”

Section: Applications Of Exosomes To Cancer Diagnostics and Therapymentioning

confidence: 99%

Formation and role of exosomes in cancer

Brinton

Sloane

Kester

et al. 2014

Cell. Mol. Life Sci.

207

172

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Exosomes offer new insight into cancer biology with both diagnostic and therapeutic implications. Because of their cell-to-cell communication, exosomes influence tumor progression, metastasis, and therapeutic efficacy. They can be isolated from blood and other bodily fluids to reveal disease processes occurring within the body, including cancerous growth. In addition to being a reservoir of cancer biomarkers, they can be re-engineered to reinstate tumor immunity. Tumor exosomes interact with various cells of the microenvironment to confer tumor-advantageous changes that are responsible for stromal activation, induction of the angiogenic switch, increased vascular permeability, and immune escape. Exosomes also contribute to metastasis by aiding in the epithelial-tomesenchymal transition and formation of the pre-metastatic niche. Furthermore, exosomes protect tumor cells from the cytotoxic effects of chemotherapy drugs and transfer chemoresistance properties to nearby cells. Thus, exosomes are essential to many lethal elements of cancer and it is important to understand their biogenesis and role in cancer.

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“…The extracellular vesicles produced by SFTS virus NSs-expressing cells and SFTS virus-infected cells displayed markers characteristic of exosomes, such as being positive for the tetraspanin CD63, a widely used exosome marker (46). Interestingly, we also found that the extracellular vesicles preferentially contain LC3-I rather than LC3-II.…”

Section: Discussionmentioning

confidence: 50%

Extracellular Vesicles Mediate Receptor-Independent Transmission of Novel Tick-Borne Bunyavirus

Silvas

Popov

Paulucci-Holthauzen

et al. 2016

J Virol

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Severe fever with thrombocytopenia syndrome (SFTS) virus is a newly recognized member of the genus Phlebovirus in the family Bunyaviridae. The virus was isolated from patients presenting with hemorrhagic manifestations and an initial case fatality rate of 12 to 30% was reported. Due to the recent emergence of this pathogen, there is limited knowledge on the molecular virology of SFTS virus. Recently, we reported that the SFTS virus NSs protein inhibited the activation of the beta interferon (IFN-␤) promoter. Furthermore, we also found that SFTS virus NSs relocalizes key components of the IFN response into NSs-induced cytoplasmic structures. Due to the important role these structures play during SFTS virus replication, we conducted live cell imaging studies to gain further insight into the role and trafficking of these cytoplasmic structures during virus infection. We found that some of the SFTS virus NSs-positive cytoplasmic structures were secreted to the extracellular space and endocytosed by neighboring cells. We also found that these secreted structures isolated from NSs-expressing cells and SFTS virus-infected cells were positive for the viral protein NSs and the host protein CD63, a protein associated with extracellular vesicles. Electron microscopy studies also revealed that the isolated CD63-immunoprecipitated extracellular vesicles produced during SFTS virus infection contained virions. The virions harbored within these structures were efficiently delivered to uninfected cells and were able to sustain SFTS virus replication. Altogether, these results suggest that SFTS virus exploits extracellular vesicles to mediate virus receptor-independent transmission to host cells and open the avenue for novel therapeutic strategies against SFTS virus and related pathogens. IMPORTANCESFTS virus is novel bunyavirus associated with hemorrhagic fever illness. Currently, limited information is available about SFTS virus. In the present study, we demonstrated that extracellular vesicles produced by SFTS virus-infected cells harbor infectious virions. We sought to determine whether these "infectious" extracellular vesicles can mediate transmission of the virus and confirmed that the SFTS virions were efficiently transported by these secreted structures into uninfected cells and were able to sustain efficient replication of SFTS virus. These results have significant impact on our understanding of how the novel tick-borne phleboviruses hijack cellular machineries to establish infection and point toward a novel mechanism for virus replication among arthropod-borne viruses. The Bunyaviridae family comprises five genera, including Orthobunyavirus, Phlebovirus, Nairovirus, Hantavirus, and Tospovirus. The majority of viruses within this family (with the exception of Hantaviruses) are considered arthropod-borne viruses and are important causes of morbidity and mortality around the world. These viruses are associated with a range of clinical symptoms characterized by febrile illness and in the most severe cases fatal hepa...

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Exosomes as Immunotheranostic Nanoparticles

Cited by 89 publications

References 54 publications

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system

Formation and role of exosomes in cancer

Extracellular Vesicles Mediate Receptor-Independent Transmission of Novel Tick-Borne Bunyavirus

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