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      A Review of Biomimetic Nanoparticle Drug Delivery Systems Based on Cell Membranes

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          Cancers have always been an intractable problem because of recurrence and drug resistance. In the past few decades, nanoparticles have been explored intensely to diagnose, prevent and treat malignancy due to their good penetrability and better targeting. However, most nanocarriers have poor biodegradation and can be discharged out of the body quickly or cleared by immune cells while failing to obtain effective drug concentration at the specific sites. The emergence of biological membrane encapsulation technology relieves the fast clearance of antitumor drugs and reduces toxicity in vivo. This review will discuss the advantages and disadvantages of several blood cell membrane-coated nanoparticles and further introduce exosome-carried drugs to evidence the promising prospect of biomimetic nanoparticle drug delivery systems.

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          Most cited references 54

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          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            Using exosomes, naturally-equipped nanocarriers, for drug delivery.

             Elena Batrakova (corresponding) ,  Myung Soo Kim (2015)
            Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations.
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              Exosomes Facilitate Therapeutic Targeting of Oncogenic Kras in Pancreatic Cancer

              Summary The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes, extracellular vesicles generated by all cells, are naturally present in the blood. Here we demonstrate that enhanced retention of exosomes in circulation, compared to liposomes, is due to CD47 mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry siRNA or shRNA specific to oncogenic KRASG12D (iExosomes), a common mutation in pancreatic cancer. Compared to liposomes, iExosomes target oncogenic Kras with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. iExosomes treatment suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased their overall survival. Our results inform on a novel approach for direct and specific targeting of oncogenic Kras in tumors using iExosomes.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                14 December 2020
                : 14
                : 5495-5503
                [1 ]Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University , Nanjing, Jiangsu Province 210009, People’s Republic of China
                [2 ] Jinling Hospital Department of Blood Transfusion, School of Medicine, Nanjing University , Nanjing, Jiangsu Province 210002, People’s Republic of China
                Author notes
                Correspondence: Baoan Chen Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University , Dingjiaqiao 87, Gulou District, Nanjing, Jiangsu Province210009, People’s Republic of ChinaTel +86 25 83 27 2006Fax +86 25 83 27 2011 Email cba8888@hotmail.com
                © 2020 Zhang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 3, Tables: 1, References: 54, Pages: 9


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