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      Milk exosomes: Nature's abundant nanoplatform for theranostic applications

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          Abstract

          Exosomes are a unique subpopulation of naturally occurring extracellular vesicles which are smaller intracellular membrane nanoparticle vesicles. Exosomes have proven to be excellent nanocarriers for carrying lipids, proteins, mRNAs, non-coding RNAs, and DNAs, and disseminating long-distance intercellular communications in various biological processes. Among various cell-line or biological fluid derived exosomes, milk exosomes are abundant in nature and exhibit many nanocarrier characteristics favorable for theranostic applications. To be an effective delivery carrier for their clinical translation, exosomes must inbuilt loading, release, targeting, and imaging/tracking characteristics. Considering the unmet gaps of milk exosomes in theranostic technology it is essential to focus the current review on drug delivery and imaging applications. This review delineates the efficiency of exosomes to load therapeutic or imaging agents and their successful delivery approaches. It is emphasized on possible modifications of exosomes towards increasing the stability and delivery of agents. This article also summarizes the specific applications and the process of developing milk exosomes as a future pharmaceutical drug delivery vehicle.

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          Highlights

          • Milk exosomes are nature's abundant drug delivery carriers.

          • These exosomes exhibit superior stability, biocompatibility, half-life, and very low immunogenicity.

          • This work describes isolation methods, drug/imaging agents loading, and therapeutic implications of milk exosomes.

          • Engineered milk exosomes offer superior theranostic applications.

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          Most cited references111

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          Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis

          The use of extracellular vesicles, specifically exosomes, as carriers of biomarkers in extracellular spaces has been well demonstrated. Despite their promising potential, the use of exosomes in the clinical setting is restricted due to the lack of standardization in exosome isolation and analysis methods. The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used. A thorough understanding of the isolation and analysis methods currently being used could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.
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            Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles

            Secreted membrane-enclosed vesicles, collectively called extracellular vesicles (EVs), which include exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies and other EV subsets, encompass a very rapidly growing scientific field in biology and medicine. Importantly, it is currently technically challenging to obtain a totally pure EV fraction free from non-vesicular components for functional studies, and therefore there is a need to establish guidelines for analyses of these vesicles and reporting of scientific studies on EV biology. Here, the International Society for Extracellular Vesicles (ISEV) provides researchers with a minimal set of biochemical, biophysical and functional standards that should be used to attribute any specific biological cargo or functions to EVs.
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              Exosomes as drug delivery vehicles for Parkinson's disease therapy.

              Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson's disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100-200nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                02 February 2021
                August 2021
                02 February 2021
                : 6
                : 8
                : 2479-2490
                Affiliations
                [a ]Department of Immunology and Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX, 78504, USA
                [b ]South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, 78504, USA
                Author notes
                []Corresponding author. Department of Immunology and Microbiology Member, South Texas Center of Excellence in Cancer Research School of Medicine, The University of Texas Rio Grande Valley, 5300 North L Street, McAllen, TX, 78504, USA. murali.yallapu@ 123456utrgv.edu
                Article
                S2452-199X(21)00013-X
                10.1016/j.bioactmat.2021.01.009
                7856328
                33553829
                c0b6b286-b0b6-497a-b641-84a74a51d6c2
                © 2021 [The Author/The Authors]

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 October 2020
                : 21 December 2020
                : 8 January 2021
                Categories
                Article

                milk exosomes,extracellular vesicles,drug delivery,imaging agents,theranostic applications

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