外泌体的提取方法及其在药物递送系统中的应用
|
摘要
外泌体是一种活细胞产生的直径为40～150 nm微小囊泡,通过携带的蛋白质、脂类、RNA等参与细胞间的信息交流和物质交换。因不同生理状态下产生的外泌体作用不同,现其被广泛应用于临床肿瘤的诊断和治疗。另外,外泌体作为内源性的天然纳米材料,在药物的递送中也有着独特的优势。外泌体能更好地应用于各领域的前提是产量和纯度有所保证。因此,该文就外泌体的提取方法及其在药物递送系统中的应用做一介绍。
Exosomes are naturally nanometer-sized( 40-100 nm) vesicles that contribute to the communication among the cells through the proteins,lipids and RNA which they carried.Exosomes derived at different physiological conditions play different role,which therefore can be widely used in the diagnosis and treatment of cancer. Besides,exosomes as the natural nanomaterials have the unique advantage in drug delivery system. Although the intrinsic advantages of exosomes have evoked a surge of interest,improvements in standardized isolation techniques with high efficiency and robust yield are still a huge challenge.Here,we provide an overview of the isolation and the application of exosomes in drug delivery system.
Exosomes are naturally nanometer-sized( 40-100 nm) vesicles that contribute to the communication among the cells through the proteins,lipids and RNA which they carried.Exosomes derived at different physiological conditions play different role,which therefore can be widely used in the diagnosis and treatment of cancer. Besides,exosomes as the natural nanomaterials have the unique advantage in drug delivery system. Although the intrinsic advantages of exosomes have evoked a surge of interest,improvements in standardized isolation techniques with high efficiency and robust yield are still a huge challenge.Here,we provide an overview of the isolation and the application of exosomes in drug delivery system.
引文
[1] 李超,戴敏. 不同细胞来源的EXOs在动脉粥样硬化中的研究进展[J]. 中国药理学通报,2017,33(1):27-32.[1] Li C, Dai M. Research progress of different cell derived extracellular bodies in atherosclerosis [J]. Chin Pharmacol Bull, 2017,33(1):27-32.
[2] Vader P, Mol E A, Pasterkamp G, et al. Extracellular vesicles for drug delivery[J]. Adv Drug Deliv Rev, 2016, 106(Pt A): 148-56.
[3] Gholizadeh S, Shehata Draz M, Zarghooni M, et al. Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles: current status and future directions[J]. Biosens Bioelectron, 2017, 91: 588-605.
[4] Yang T, Martin P, Fogarty B, et al. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio[J]. Pharm Res, 2015, 32(6): 2003-14.
[5] Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes[J]. Nat Biotechnol, 2011, 29(4): 341-5.
[6] Sun X R, Zhang L C, Shi Q W, et al. Advance in research on cell-derived nanom-edicine delivery s ystem[J]. Acta Pharm Sin, 2017,52(7):1110-6.
[7] Stone D. Novel viral vector systems for gene therapy[J]. Viruses, 2010, 2(4): 1002-7.
[8] Nayerossadat N, Maedeh T, Ali P A. Viral and nonviral delivery systems for gene delivery[J]. Adv Biomed Res, 2012,1:27.
[9] Clayton A, Harris C L, Court J, et al. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59 [J]. Eur J Immunol, 2003,33(2):522-31.
[10] Haney M J, Klyachko N L, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy [J]. J Control Release, 2015,207:18-30.
[11] Viaud S, Ploix S, Lapierre V,et al. Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-γ [J]. J Immunother, 2011,34(1):65-75.
[12] Théry C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids [J]. Curr Protoc Cell Biol, 2006,Chapter 3:Unit 3.22.
[13] Mol E A, Goumans M J, Doevendans P A, et al. Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation [J]. Nanomedicine, 2017,13(6):2061-5.
[14] Zarovni N, Corrado A, Guazzi P, et al. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches [J]. Methods, 2015,87:46-58.
[15] Palma J, Yaddanapudi S C, Pigati L, et al. MicroRNAs are exported from malignant cells incustomized particles[J]. Nucleic Acids Res, 2012,40(18):9125-38.
[16] Wang J, Li W, Zhang L, et al. Chemically edited exosomes with dual ligand purified by microfluidic device for active targeted drug delivery to tumor cells[J]. ACS Appl Mater Interfaces, 2017,9(33):27441-52.
[17] Wunsch B H, Smith J T, Gifford S M, et al. Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm [J]. Nat Nanotechnol, 2016,11(11):936-40.
[18] Didiot M C, Hall L M, Coles A H, et al. Exosome-mediated delivery of hydrophobically modified siRNA for huntingtin mRNA silencing[J]. Mol Ther, 2016,24(10):1836-47.
[19] Buscail L. Pancreatic cancer: exosomes for targeting KRAS in the treatment of pancreatic cancer[J]. Nat Rev Gastroenterol Hepatol, 2017,14(11):636-8.
[20] Yim N, Ryu S W, Choi K, et al. Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module[J]. Nat Commun, 2016,7:12277.
[21] Ascucci L, Coccè V, Bonomi A, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery [J]. J Control Release, 2014,192:262-70.
[22] Yuan D, Zhao Y, Banks W A, et al. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain[J]. Biomaterials, 2017,142:1-12.
[23] Agrawal A K, Aqil F, Jeyabalan J, et al. Milk-derived exosomes for oral delivery of paclitaxel[J]. Nanomedicine, 2017,13(5):1627-36.
[24] Wang Y Y, Chen X J, Tian B Q, et al. Nucleolin-targeted extracellular vesicles as a versatile platform for biologics delivery to breast cancer[J]. Theranostics, 7(5): 1360-72.
[25] Hadla M, Palazzolo S, Corona G, et al. Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancermouse models[J]. Nanomedicine (Lond), 2016,11(18):2431-41.
[2] Vader P, Mol E A, Pasterkamp G, et al. Extracellular vesicles for drug delivery[J]. Adv Drug Deliv Rev, 2016, 106(Pt A): 148-56.
[3] Gholizadeh S, Shehata Draz M, Zarghooni M, et al. Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles: current status and future directions[J]. Biosens Bioelectron, 2017, 91: 588-605.
[4] Yang T, Martin P, Fogarty B, et al. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio[J]. Pharm Res, 2015, 32(6): 2003-14.
[5] Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes[J]. Nat Biotechnol, 2011, 29(4): 341-5.
[6] Sun X R, Zhang L C, Shi Q W, et al. Advance in research on cell-derived nanom-edicine delivery s ystem[J]. Acta Pharm Sin, 2017,52(7):1110-6.
[7] Stone D. Novel viral vector systems for gene therapy[J]. Viruses, 2010, 2(4): 1002-7.
[8] Nayerossadat N, Maedeh T, Ali P A. Viral and nonviral delivery systems for gene delivery[J]. Adv Biomed Res, 2012,1:27.
[9] Clayton A, Harris C L, Court J, et al. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59 [J]. Eur J Immunol, 2003,33(2):522-31.
[10] Haney M J, Klyachko N L, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy [J]. J Control Release, 2015,207:18-30.
[11] Viaud S, Ploix S, Lapierre V,et al. Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-γ [J]. J Immunother, 2011,34(1):65-75.
[12] Théry C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids [J]. Curr Protoc Cell Biol, 2006,Chapter 3:Unit 3.22.
[13] Mol E A, Goumans M J, Doevendans P A, et al. Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation [J]. Nanomedicine, 2017,13(6):2061-5.
[14] Zarovni N, Corrado A, Guazzi P, et al. Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches [J]. Methods, 2015,87:46-58.
[15] Palma J, Yaddanapudi S C, Pigati L, et al. MicroRNAs are exported from malignant cells incustomized particles[J]. Nucleic Acids Res, 2012,40(18):9125-38.
[16] Wang J, Li W, Zhang L, et al. Chemically edited exosomes with dual ligand purified by microfluidic device for active targeted drug delivery to tumor cells[J]. ACS Appl Mater Interfaces, 2017,9(33):27441-52.
[17] Wunsch B H, Smith J T, Gifford S M, et al. Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm [J]. Nat Nanotechnol, 2016,11(11):936-40.
[18] Didiot M C, Hall L M, Coles A H, et al. Exosome-mediated delivery of hydrophobically modified siRNA for huntingtin mRNA silencing[J]. Mol Ther, 2016,24(10):1836-47.
[19] Buscail L. Pancreatic cancer: exosomes for targeting KRAS in the treatment of pancreatic cancer[J]. Nat Rev Gastroenterol Hepatol, 2017,14(11):636-8.
[20] Yim N, Ryu S W, Choi K, et al. Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module[J]. Nat Commun, 2016,7:12277.
[21] Ascucci L, Coccè V, Bonomi A, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery [J]. J Control Release, 2014,192:262-70.
[22] Yuan D, Zhao Y, Banks W A, et al. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain[J]. Biomaterials, 2017,142:1-12.
[23] Agrawal A K, Aqil F, Jeyabalan J, et al. Milk-derived exosomes for oral delivery of paclitaxel[J]. Nanomedicine, 2017,13(5):1627-36.
[24] Wang Y Y, Chen X J, Tian B Q, et al. Nucleolin-targeted extracellular vesicles as a versatile platform for biologics delivery to breast cancer[J]. Theranostics, 7(5): 1360-72.
[25] Hadla M, Palazzolo S, Corona G, et al. Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancermouse models[J]. Nanomedicine (Lond), 2016,11(18):2431-41.