Engineered exosomes: desirable target-tracking characteristics for cerebrovascular and neurodegenerative disease therapies


Posted: 2021-09-15 19:00:00
Review Theranostics . 2021 Aug 18;11(18):8926-8944. doi: 10.7150/thno.62330. eCollection 2021. Affiliations Expand Affiliations 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China. 2 Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China. Item in Clipboard Review Meng Xu et al. Theranostics. 2021. Show details Display options Display options Format Theranostics . 2021 Aug 18;11(18):8926-8944. doi: 10.7150/thno.62330. eCollection 2021. Affiliations 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China. 2 Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China. Item in Clipboard CiteDisplay options Display options Format Abstract As extracellular vesicles secreted by cells, exosomes are intercellular signalosomes for cell communication and pharmacological effectors. Because of their special properties, including low toxicity and immunogenicity, biodegradability, ability to encapsulate endogenous biologically active molecules and cross the blood-brain barrier (BBB), exosomes have great therapeutic potential in cerebrovascular and neurodegenerative diseases. However, the poor targeting ability of natural exosomes greatly reduces the therapeutic effect. Using engineering technology, exosomes can obtain active targeting ability to accumulate in specific cell types and tissues by attaching targeting units to the membrane surface or loading them into cavities. In this review, we outline the improved targeting functions of bioengineered exosomes, tracing and imaging techniques, administration methods, internalization in the BBB, and therapeutic effects of exosomes in cerebrovascular and neurodegenerative diseases and further evaluate the clinical opportunities and challenges in this research field. Keywords: administration routes; brain targeting; cerebrovascular disease; engineered exosomes; neurological disorders; tracking. © The author(s). Conflict of interest statement Competing Interests: The authors have declared that no competing interest exists. Figures Figure 1 Schematic presentation of the use… Figure 1 Schematic presentation of the use of engineered exosomes as novel therapeutic tools for… Figure 1 Schematic presentation of the use of engineered exosomes as novel therapeutic tools for brain targeting against cerebrovascular and neurodegenerative diseases. Exosomes can be extracted from a wide range of sources, including immune and cancer cell lines, blood, tears, urine, saliva, milk, ascites, eukaryotes, prokaryotes, herbs, et al. This review mainly introduces the administration routes, engineering targeting strategy, therapeutic effects, labeling and tracking methods of exosomes. Figure 2 The route and mechanism by… Figure 2 The route and mechanism by which exosomes transport across BBB. Brain microvessels endothelial… Figure 2 The route and mechanism by which exosomes transport across BBB. Brain microvessels endothelial cells (ECs) are the bricks supporting the BBB phenotype. On the one hand, exosomes can be internalized by ECs and penetrate the BBB. On the other hand, the internalization of exosomes can improve the integrity of BBB. Figure 3 Common exosome engineering strategies. (A)… Figure 3 Common exosome engineering strategies. (A) Genetic engineering: the foreign gene is transferred into… Figure 3 Common exosome engineering strategies. (A) Genetic engineering: the foreign gene is transferred into the target cell by plasmid, so that the exosomes can carry specific targeted proteins or peptides. a. BM-MSCs were genetically engineered to secrete exosomes expressing rabies virus glycoprotein (RVG) fused Lamp2b to achieve targeted delivery of gene drugs to the brain (adapted with permission from , copyright 2017 Elsevier). (B) Biochemical engineering: using biochemical conjugation or hydrophobic insertion or chemical coupling to conjugate functional ligands to exosomes. b. The surface of MSC-derived exosomes was conjugated with targeting peptide through bio-orthogonal chemistry method (adapted with permission from , copyright 2018 Elsevier). (C) Physical targeting: loading magnetic particles to make exosomes accumulate at the target site. c. Magnetic nanovesicles (MNV) containing iron oxide nanoparticles (IONP) were prepared to achieve magnetic navigation mediated accumulation (adapted with permission from , copyright 2020 Elsevier). Figure 4 The therapeutic role of exosomes… Figure 4 The therapeutic role of exosomes derived from various cell sources have been used… Figure 4 The therapeutic role of exosomes derived from various cell sources have been used to treat cerebrovascular and neurodegenerative diseases. Figure 5 Imaging strategies for exosomes in… Figure 5 Imaging strategies for exosomes in vivo tracking. Various strategies have been developed to… Figure 5 Imaging strategies for exosomes in vivo tracking. Various strategies have been developed to elucidate exosome trafficking and selective targeting in vivo. This will contribute to a better understanding of the biological role of exosomes and their potential as natural drug carriers. (A) Exosomes were successfully labeled with Gaussia luciferase-lactadherin fusion protein (adapted with permission from , copyright 2013 Elsevier). (B) Ex vivo fluorescent imaging and in vivo CT imaging of MSC-exo using PKH-26 and gold nanoparticles as labeling agents (adapted with permission from , copyright 2019 American Chemical Society). (C) 99mTc-hexamethylpropyleneamineoxime (HMPAO) was chosen as a proper radiotracer to monitor Exosome-mimetic nanovesicles (ENVs) (adapted with permission from , copyright 2015 Springer Nature). References Cai YC, Liu WY, Lian L, Xu YZ, Bai XD, Xu SX. et al. Stroke treatment: Is exosome therapy superior to stem cell therapy? Biochimie. 2020;179:190–204. - PubMed Joe E, Ringman JM. Cognitive symptoms of Alzheimer's disease: Clinical management and prevention. Br Med J. 2019. 367. Loureiro JA, Gomes B, Fricker G, Coelho MAN, Rocha S, Pereira MC. Cellular uptake of plga nanoparticles targeted with anti-amyloid and anti-transferrin receptor antibodies for Alzheimer's disease treatment. Colloids Surf B Biointerfaces. 2016;145:8–13. - PubMed Dal Magro R, Ornaghi F, Cambianica I, Beretta S, Re F, Musicanti C. et al. Apoe-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier. J Control Release. 2017;249:103–10. - PubMed Zhao CY, Zhang JL, Hu HY, Qiao MX, Chen DW, Zhao XL. et al. Design of lactoferrin modified lipid nano-carriers for efficient brain-targeted delivery of nimodipine. Mater Sci Eng C Mater Biol Appl. 2018;92:1031–40. - PubMed Show all 157 references Publication types

参考サイト PubMed: exsome



バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
3月 07, 2019 バイオアソシエイツ

新研究で分娩にエクソソームが重要な役割を果たすことが示めされた

テキサス大学メディカルブランチ(UTMB)のRamkumar Menon博士が率いる研究者グループは、まだ確実ではないが分娩のタイミングにおけるキープレイヤーについて新たな洞察を見出した。この新しい情報によって、科学者たちは早産を防ぐことができるようになるかもしれない。 この研究は2019年1月24日にScientific Reportsにオンラインで発表された。 このオープンアクセスの論文は「 エクソソーム はマウスで早産を引き起こす:妊娠中の傍分泌シグナル伝達の証拠(Exosomes Cause…

ゲスト 941人 と メンバー 7人 がオンラインです