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Open accessJournal ArticleDOI: 10.3389/FCELL.2021.650426

Exosome-Based Delivery of Natural Products in Cancer Therapy.

02 Mar 2021-Frontiers in Cell and Developmental Biology (Frontiers Media SA)-Vol. 9, pp 650426-650426
Abstract: A rapidly growing research evidence has begun to shed light on the potential application of exosome, which modulates intercellular communications. As donor cell released vesicles, exosomes could play roles as a regulator of cellular behaviors in up-taken cells, as well as a delivery carrier of drugs for targeted cells. Natural product is an invaluable drug resources and it is used widely as therapeutic agents in cancers. This review summarizes the most recent advances in exosomes as natural product delivery carriers in cancer therapy from the following aspects: composition of exosomes, biogenesis of exosomes, and its functions in cancers. The main focus is the advantages and applications of exosomes for drug delivery in cancer therapy. This review also summarizes the isolation and application of exosomes as delivery carriers of natural products in cancer therapy. The recent progress and challenges of using exosomes as drug delivery vehicles for five representative anti-cancer natural products including paclitaxel, curcumin, doxorubicin, celastrol, and β-Elemene. Based on the discussion on the current knowledge about exosomes as delivery vehicles for drugs and natural compounds to the targeted site, this review delineates the landscape of the recent research, challenges, trends and prospects in exosomes as delivery vehicles for drugs and natural compounds for cancer treatment.

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Topics: Exosome (65%)

6 results found

Open accessJournal ArticleDOI: 10.2147/IJN.S313912
Qi Li1, Suna Cai1, Mengjiao Li1, Kab Ibrahim Salma1  +4 moreInstitutions (2)
Abstract: Nowadays, tumor has been the serious threat to human health and life. To further explore the mechanism of tumor genesis and development is necessarily for developing the effective treatment strategy. Extracellular vesicles are the vesicles secreted by almost all types of cells, and they play an important part in intercellular communication by transporting their cargoes. Immune cells are the vital components of the human defense system, which defense against infection and tumor through cytotoxicity, immune surveillance, and clearance. However, via release tumor-derived extracellular vesicles, tumor could induce immune cells dysfunction to facilitate its proliferation and metastasis. Studies have shown that tumor-derived extracellular vesicles play dual role on immune cells by their specific cargoes. Here, we reviewed the effects of tumor-derived extracellular vesicles on immune cells in recent years and also summarized their research progress in the tumor immunotherapy and diagnosis.

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Topics: Immune system (56%), Tumor-Derived (55%), Immunotherapy (54%)

2 Citations

Open accessJournal ArticleDOI: 10.3389/FCELL.2021.733751
Shuang Wu1, Tianye Li1, Weiwei Liu2, Yongye Huang1Institutions (2)
Abstract: Cell death induction has become popular as a novel cancer treatment. Ferroptosis, a newly discovered form of cell death, features regulated, iron-dependent accumulation of lipid hydroperoxides. Since this word "ferroptosis" was coined, numerous studies have examined the complex relationship between ferroptosis and cancer. Here, starting from the intrinsic hallmarks of cancer and cell death, we discuss the theoretical basis of cell death induction as a cancer treatment. We review various aspects of the relationship between ferroptosis and cancer, including the genetic basis, epigenetic modification, cancer stem cells, and the tumor microenvironment, to provide information and support for further research on ferroptosis. We also note that exosomes can be applied in ferroptosis-based therapy. These extracellular vesicles can deliver different molecules to modulate cancer cells and cell death pathways. Using exosomes to control ferroptosis occurring in targeted cells is promising for cancer therapy.

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Topics: Cancer stem cell (54%), Cancer (50%)

1 Citations

Open accessJournal ArticleDOI: 10.1080/14737175.2021.1965882
Emily Dexter1, Qingzhong Kong1Institutions (1)
Abstract: Introduction: The cellular prion protein (PrPC), some of its derivatives (especially PrP N-terminal N1 peptide and shed PrP), and PrPC-containing exosomes have strong neuroprotective activities, which have been reviewed in the companion article (Part I) and are briefly summarized here.Areas covered: We propose that elevating the extracellular levels of a protective PrP form using gene therapy and other approaches is a very promising novel avenue for prophylactic and therapeutic treatments against prion disease, Alzheimer's disease, and several other neurodegenerative diseases. We will dissect the pros and cons of various potential PrP-based treatment options and propose a few strategies that are more likely to succeed. The cited references were obtained from extensive PubMed searches of recent literature, including peer-reviewed original articles and review articles.Expert opinion: Concurrent knockdown of celllular PrP expression and elevation of the extracellular levels of a neuroprotective PrP N-terminal peptide via optimized gene therapy vectors is a highly promising broad-spectrum prophylactic and therapeutic strategy against several neurodegenerative diseases, including prion diseases, Alzheimer's disease and Parkinson's disease.

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1 Citations

Journal ArticleDOI: 10.1016/J.JCHROMB.2021.122899
Fang Chen1, Zheng Yu1, Xianqin Wang1Institutions (1)
Abstract: In this study, we used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to measure the concentration of narciclasine and 7-deoxynarciclasine in mouse blood after intravenous (i.v.) and oral administration (p.o.), and we used this method to investigate their pharmacokinetics profiles in mice. Chromatographic separation of the analytes was achieved using a UPLC HSS T3 column (2.1 mm × 100 mm, 1.8 μm) with a mobile phase consisting of acetonitrile–water (0.1% formic acid) by gradient elution. Electrospray ionization (ESI positive-ion mode)-tandem mass spectrometry in multiple reaction monitoring (MRM) mode was employed for quantitative analysis of the analytes in mouse blood samples. Twelve mice were administered narciclasine and 7-deoxynarciclasine (2 mg/kg) intravenously (iv), while the other twelve mice were administered narciclasine and 7-deoxynarciclasine (10 mg/kg) orally. The mouse blood was withdrawn from the caudal vein to be processed, after which the blood was analyzed by UPLC-MS/MS, and the corresponding data were fitted using the Drug and Statistics (DAS) software. Standard curves of narciclasine and 7-deoxynarciclasine were generated over the concentration range of 5–5000 ng/mL. The intra-day accuracy of narciclasine and 7-deoxynarciclasine was 90–105%, and the corresponding inter-day accuracy was 87–108%. The intra-day precision was less than 13%, while the inter-day precision was less than 14%. Matrix effects were also observed (between 94% and 104%), and the recovery calculated was higher than 70%. The developed and validated UPLC-MS/MS method was then successfully applied in determining the mouse pharmacokinetics of narciclasine and 7-deoxynarciclasine. From this, the bioavailability of narciclasine and 7-deoxynarciclasine was determined to be 10.3% and 35.4%, respectively.

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Topics: Narciclasine (64%)

Open accessJournal ArticleDOI: 10.1016/J.INTIMP.2021.107960
Hanren Chen1, Shulian Jiang, Peng Zhang1, Zhongyu Ren1  +1 moreInstitutions (1)
Abstract: Background Hepatocellular carcinoma (HCC) is easy to relapse after resection for its lack of anti-tumor immunity due to pro-tumorigenesis by promoting M2 type macrophage polarization. Recent studies have shown that exosomes are closely related to the occurrence and development of HCC. Antigenic exosomes from HCC are able to polarize into alternatively activated macrophages M2, but do not stimulate M1 macrophages polarization. Iron oxide nanoparticles (IONs) have been demonstrated to be able to promote M1 macrophages polarization. This research was to explore exosomes as vehicles to synergize with pegylated IONs loaded with chlorin e6 (PIONs@E6) to enhance their immunity against HCC via promoting M1 macrophages polarization. Materials and Methods PIONs@E6 was synthesized and then characterized by chemico-physical analysis, transmission electron microscope (TEM), respectively. After characterization of PIONs-contained exosomes by TEM, and then the exosomal surface specific molecules CD9 and CD63 were determined by Western Blotting assay. Markers of M1 macrophage polarization in vitro and in vivo were analyzed by enzyme linked immunosorbent assay (ELISA) and flow cytometry, respectively. Intracellular reactive oxygen species (ROS) in macrophages were analyzed using a Spectra Max fluorescence microplate reader. Inhibitory effect of PIONs-contained exosomes on HCC was evaluated by monitoring tumor growth in an in vivo xenograft mice model. Results PIONs@E6 showed good water solubility with a core diameter around 10 nm and a hydrate diameter around 37 nm. The expression of exosome specific markers CD9 and CD63 was kept at a high level. PIONs-contained exosomes can dose-dependently promote M1 macrophages polarization in vitro and in vivo. Of note, PIONs-contained exosomes could initiate a significantly higher level of ROS in macrophages and remarkably inhibit the tumor growth in mice bearing HCC xenograft. Conclusion Exosomes as vehicles could be synergized with PIONs@E6 to enhance their immunity against HCC via promoting M1 macrophages polarization.

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Topics: Exosome (61%), Macrophage polarization (57%), Microvesicles (51%)


117 results found

Open accessJournal ArticleDOI: 10.1016/J.EJCA.2012.12.027
Abstract: Introduction: Cancer incidence and mortality estimates for 25 cancers are presented for the 40 countries in the four United Nations-defined areas of Europe and for the European Union (EU-27) for 2012. Methods: We used statistical models to estimate national incidence and mortality rates in 2012 from recently-published data, predicting incidence and mortality rates for the year 2012 from recent trends, wherever possible. The estimated rates in 2012 were applied to the correspond- ing population estimates to obtain the estimated numbers of new cancer cases and deaths in Europe in 2012. Results: There were an estimated 3.45 million new cases of cancer (excluding non-melanoma skin cancer) and 1.75 million deaths from cancer in Europe in 2012. The most common cancer sites were cancers of the female breast (464,000 cases), followed by colorectal (447,000), pros- tate (417,000) and lung (410,000). These four cancers represent half of the overall burden of cancer in Europe. The most common causes of death from cancer were cancers of the lung (353,000 deaths), colorectal (215,000), breast (131,000) and stomach (107,000). In the Euro- pean Union, the estimated numbers of new cases of cancer were approximately 1.4 million

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Topics: European union (59%), Mortality rate (58%), Cancer (58%) ... read more

4,476 Citations

Open accessJournal ArticleDOI: 10.1002/0471143030.CB0322S30
Abstract: Exosomes are small membrane vesicles found in cell culture supernatants and in different biological fluids. Exosomes form in a particular population of endosomes, called multivesicular bodies (MVBs), by inward budding into the lumen of the compartment. Upon fusion of MVBs with the plasma membrane, these internal vesicles are secreted. Exosomes possess a defined set of membrane and cytosolic proteins. The physiological function of exosomes is still a matter of debate, but increasing results in various experimental systems suggest their involvement in multiple biological processes. Because both cell-culture supernatants and biological fluids contain different types of lipid membranes, it is critical to perform high-quality exosome purification. This unit describes different approaches for exosome purification from various sources, and discusses methods to evaluate the purity and homogeneity of the purified exosome preparations.

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Topics: Exosome (69%), Exosomal secretion (52%), Circulating microvesicle (52%) ... read more

3,640 Citations

Open accessJournal ArticleDOI: 10.1038/NBT.3330
Elvin Blanco1, Haifa Shen2, Haifa Shen1, Mauro Ferrari2  +1 moreInstitutions (2)
Abstract: Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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3,304 Citations

Journal ArticleDOI: 10.1038/NBT.1807
Lydia Alvarez-Erviti1, Yiqi Seow1, HaiFang Yin1, Corinne A. Betts1  +2 moreInstitutions (1)
Abstract: To realize the therapeutic potential of RNA drugs, efficient, tissue-specific and nonimmunogenic delivery technologies must be developed. Here we show that exosomes-endogenous nano-vesicles that transport RNAs and proteins-can deliver short interfering (si)RNA to the brain in mice. To reduce immunogenicity, we used self-derived dendritic cells for exosome production. Targeting was achieved by engineering the dendritic cells to express Lamp2b, an exosomal membrane protein, fused to the neuron-specific RVG peptide. Purified exosomes were loaded with exogenous siRNA by electroporation. Intravenously injected RVG-targeted exosomes delivered GAPDH siRNA specifically to neurons, microglia, oligodendrocytes in the brain, resulting in a specific gene knockdown. Pre-exposure to RVG exosomes did not attenuate knockdown, and non-specific uptake in other tissues was not observed. The therapeutic potential of exosome-mediated siRNA delivery was demonstrated by the strong mRNA (60%) and protein (62%) knockdown of BACE1, a therapeutic target in Alzheimer's disease, in wild-type mice.

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Topics: Exosome (63%), Gene Knockdown Techniques (56%), Gene delivery (55%) ... read more

2,688 Citations

Journal ArticleDOI: 10.1016/J.CEB.2009.03.007
Mikael Simons1, Graça RaposoInstitutions (1)
Abstract: Cells release different types of vesicular carriers of membrane and cytosolic components into the extracellular space. These vesicles are generated within the endosomal system or at the plasma membrane. Among the various kinds of secreted membrane vesicles, exosomes are vesicles with a diameter of 40-100 nm that are secreted upon fusion of multivesicular endosomes with the cell surface. Exosomes transfer not only membrane components but also nucleic acid between different cells, emphasizing their role in intercellular communication. This ability is likely to underlie the different physiological and pathological events, in which exosomes from different cell origins have been implicated. Only recently light have been shed on the subcellular compartments and mechanisms involved in their biogenesis and secretion opening new avenues to understand their functions.

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Topics: Microvesicles (57%), Endosome (56%), Vesicle (54%) ... read more

1,684 Citations

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