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      Engineered extracellular vesicles as intelligent nanosystems for next-generation nanomedicine

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          Abstract

          Engineered EVs containing an intelligent core have been designed to interact with a living host environment and function in an ideal situation. This review provides a new insight into design of next-generation EV-based theranostic platforms.

          Abstract

          Extracellular vesicles (EVs), as natural carriers of bioactive cargo, have a unique micro/nanostructure, bioactive composition, and characteristic morphology, as well as fascinating physical, chemical and biochemical features, which have shown promising application in the treatment of a wide range of diseases. However, native EVs have limitations such as lack of or inefficient cell targeting, on-demand delivery, and therapeutic feedback. Recently, EVs have been engineered to contain an intelligent core, enabling them to (i) actively target sites of disease, (ii) respond to endogenous and/or exogenous signals, and (iii) provide treatment feedback for optimal function in the host. These advances pave the way for next-generation nanomedicine and offer promise for a revolution in drug delivery. Here, we summarise recent research on intelligent EVs and discuss the use of “intelligent core” based EV systems for the treatment of disease. We provide a critique about the construction and properties of intelligent EVs, and challenges in their commercialization. We compare the therapeutic potential of intelligent EVs to traditional nanomedicine and highlight key advantages for their clinical application. Collectively, this review aims to provide a new insight into the design of next-generation EV-based theranostic platforms for disease treatment.

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          Most cited references376

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

            ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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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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                Author and article information

                Contributors
                Journal
                NHAOAW
                Nanoscale Horizons
                Nanoscale Horiz.
                Royal Society of Chemistry (RSC)
                2055-6756
                2055-6764
                June 27 2022
                2022
                : 7
                : 7
                : 682-714
                Affiliations
                [1 ]School of Medicine, South China University of Technology, Guangzhou 510006, P. R. China
                [2 ]Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P. R. China
                [3 ]School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen 518172, China
                [4 ]Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
                [5 ]Department of Clinical Laboratory Medicine, Tai Zhou Central Hospital (Taizhou University Hospital), Taizhou 318000, P. R. China
                [6 ]Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
                [7 ]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China
                [8 ]School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiao Tong University, Xi’an 710049, P. R. China
                Article
                10.1039/D2NH00070A
                35662310
                3a1edb74-9762-41be-a7e7-be87aed28c2c
                © 2022

                http://rsc.li/journals-terms-of-use

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