在细胞通讯过程中,细胞分泌的大小在40~100 nm之间的外泌体具有负载"货物"并将其传递给靶细胞的能力。外泌体是细胞通讯重要的调节者,当疾病发生时,外泌体的组成会发生变化,在诊断和治疗方面均具有重要作用。外泌体作为药物的天然内源性载体具有独特优势,如其免疫原性低,在血液中的稳定性高,向细胞运输药物的效率高,和更强的增强渗透滞留效应(EPR)。目前,外泌体已经成功运载基因类药物、抗癌药物和抗炎症药物等其他类型药物。作为基因类药物载体,外泌体有助于同时提高转染效率和降低副作用。作为抗癌类和抗炎症类药物载体,外泌体可较好地保护药物免遭人体清除。本文按照外泌体负载"货物"的种类综述外泌体作为药物载体的最新进展,并简要讨论构建外泌体药物运输系统所需考虑的外泌体的来源、提纯方法、载药种类、载药方式以及载药系统的使用方式等关键因素对外泌体药物运输系统的影响,展望外泌体药物运输系统临床应用所面临的挑战和可能的解决途径。
[1] Kooijmans S A A, Vader P, van Dommelen S M, van Solinge W W, Schiffelers R M. Int. J. Nanomed., 2012, 7:1525.
[2] Johnsen K B, Gudbergsson J M, Skov M N, Pilgaard L, Moos T, Duroux M. Biochimica. et. Biophysica. Acta, 2014, 1846:75.
[3] Qin J, Xu Q. Acta Pol. Pharm., 2014, 71:537.
[4] Lakhal S, Wood M J. Bioessays, 2011, 33:737.
[5] Zocco D, Ferruzzi P, Cappello F, Kuo W P, Fais S. Front. Oncol., 2014, 4:2.
[6] Jang S C, Kim O Y, Yoon C M, Choi D S, Roh T Y, Park J, Nilsson J, Lötvall J, Kim Y K, Gho Y S. ACS Nano, 2013, 7:7698.
[7] Chen L, Wang Y, Pan Y, Zhang L, Shen C, Qin G, Ashraf M, Weintraub N, Ma G, Tang Y. Biochem. Biophys. Res. Commun., 2013, 431:566.
[8] Bryniarski K, Ptak W, Jayakumar A, Püllmann K, Caplan M J, Chairoungdua A, Lu J, Adams B D, Sikora E, Nazimek K, Marquez S, Kleinstein S H, Sangwung P, Iwakiri Y, Delgato E, Redegeld F, Blokhuis B R, Wojcikowski J, Daniel A W, Kormelink T G, Askenase P W. J. Allergy Clin. Immunol., 2013, 132:170.
[9] Yu L, Yang F, Jiang L, Chen Y, Wang K, Xu F, Wei Y, Cao X, Wang J, Cai Z. Eur. J. Immunol., 2013, 43:2461.
[10] Sun D M, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang H G, Mol. Ther., 2010, 18:1606.
[11] Yousefpour P, Chilkoti A. Biotechnol. Bioeng., 2014, 111:1699.
[12] 陈孟婕(Chen M J), 姚晋荣(Yao J R), 邵正中(Shao Z Z),陈新(Chen X). 化学进展(Progress in Chemistry), 2011, 23(1):202.
[13] Kalra H, Adda C G, Liem M, Ang C S, Mechler A, Simpson R J, Hulett M D, Mathivanan S. Proteomics, 2013, 13:3354.
[14] Nakamura H, Jun F, Maeda H. Expert Opin. Drug Deliv., 2015, 12:53.
[15] Kobayashi H, Watanabe R, Choyke P L. Theranostics, 2014, 4:81.
[16] Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood M J A. Nat. Biotechnol., 2011, 29:341.
[17] Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M. Cancer Lett., 2013, 335:201.
[18] Bryniarski K, Ptak W, Jayakumar A, Püllmann K, Caplan M J, Chairoungdua A, Lu J, Adams B D, Sikora E, Nazimek K, Marquez S, Kleinstein S H, Sangwung P, Iwakiri Y, Delgato E, Redegeld F, Blokhuis B, Wojcikowski J, Daniel A W, Kormelink T G, Askenase P. J. Allergy Clin. Immunol., 2013, 132:170.
[19] Pascucci L, Coccè V, Bonomi A, Ami D, Ceccarelli P, Ciusani E, Viganò L, Locatelli A, Sisto F, Doglia S M, Parati E, Bernardo M E, Muraca M, Alessandri G, Bondiolotti G, Pessina A. J. Control Release, 2014, 192:262.
[20] Tian Y, Li S, Song J, Ji T, Zhu M, Anderson G, Wei J, Nie G. Biomaterials, 2014, 35:2383.
[21] Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H, Li G. Mol. Ther., 2008, 16:782.
[22] Mizrak A, Bolukbasi M F, Ozdener G B, Brenner G J, Madlener S, Erkan E P, Ströbel T, Breakefield X O, Saydam O. Mol. Ther., 2013, 21:101.
[23] Ohno S I, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, Fujita K, Mizutani T, Ohgi T, Ochiya T, Gotoh N, Kuroda M. Mol. Ther., 2013, 21:185.
[24] Wahlgren J, Karlson T D L,Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, Valadi H. Nucleic Acids Res., 2012, 40:e130.
[25] Shtam T A, Kovalev R A, Varfolomeeva E Y, Makarov E M, Kil Y V, Filatov M V. Cell Commun. Signal., 2013, 11:88.
[26] Gehl J. Acta Physiol. Scand, 2003, 177:437.
[27] Hood J L, Scott M J, Wickline S A. Anal. Biochem., 2014, 448:41.
[28] Lai R C, Yeo R W Y, Tan K H, Lim S K. Biotechnol. Adv., 2013, 31:543.
[29] Kosaka N, Iguchi H, Yoshiok Y, Hagiwara K, Takeshita F, Ochiya T. J. Biol. Chem., 2012, 287:1397.
[30] Rupp A K, Rupp C, Keller S, Brase J C, Ehehalt R, Fogel M, Moldenhauer G, Marmé F, Sültmann H, Altevogt P. Gynecol. Oncol., 2011, 122:437.
[31] Suresh P S, Venkatesh T, Tsutsumi R. Endocr. J., 2014, 61:655.
[32] Ibraheem D, Elaissari A, Fessi H. Int. J. Pharm., 2014, 459:70.
[33] Naidu S, Magee P, Garofalo M. J. Hematol. Oncol., 2015, 8:68.
[34] Reddy K B. Cancer Cell Int., 2015, 15:38.
[35] De Mendoza C, Barreiro P, Benitez L, Soriano V. Expert Opin. Biol. Ther., 2015, 15:319.
[36] Stan R, Zaia J A. Curr. HIV/AIDS Rep., 2014, 11:11.
[37] Bradshaw A C, Baker A H. Vasc. Pharmacol., 2013, 58:174.
[38] Williams P D, Kingston P A. Cardiovasc. Res., 2011, 91:565.
[39] Griesenbach U, Pytel K M, Alton E W F W. Hum. Gene Ther., 2015, 26:266.
[40] Armstrong D K, Cunningham S, Davies J C, Alton E W F W. Arch. Dis. Child., 2014, 99:465.
[41] Pike-Overzet K, van der Burg M, Wagemaker G, van Dongen J J M, Staal F J T. Mol. Ther., 2007, 15:1910.
[42] Guedon, J M G, Wu S B, Zheng X, Churchill C C, Glorioso J C, Liu C H, Liu S, Vulchanova L, Bekker A, Tao Y X, Kinchington P R, Goins W F f, Fairbanks C A, Hao S. Mol. Pain, 2015, 11:27.
[43] Severino P, Szymanski M, Favaro M, Azzoni A R, Chaud M V, Santana M H A, Silva A M, Souto E B. Eur. J. Pharm. Sci., 2015, 66:78.
[44] Yin H, Kanasty R L, Eltoukhy A A, Vegas A J, Dorkin J R, Anderson D G. Nat. Rev. Genet., 2014, 15:541.
[45] 张悦(Zhang Y), 于奡(Yu A), 王永健(Wang Y J). 化学进展(Progress in Chemistry), 2008, 20(5):740.
[46] Such G K, Yan Y, Johnston A P R, Gunawan S T, Caruso F. Adv. Mater., 2015, 27:2278.
[47] Pan Q, Ramakrishnaiah V, Henry S, Fouraschen S, de Ruiter P E, Kwekkeboom J, Tilanus H W, Janssen H L A, van der Laan L J W. Gut., 2012, 61:1330.
[48] Xu C F, Wang J. Asian J. Pharm. Sci., 2015, 10:1.
[49] Zhang J, Li X, Huang L. J. Control. Release, 2014, 190:440.
[50] Gary D J, Puri N, Won Y Y. J. Control. Release, 2007, 121:64.
[51] Whitehead K A, Langer R, Anderson D G. Nat. Rev.Drug Discov., 2009, 8:129.
[52] Trompeter H I, Dreesen J, Hermann E, Iwaniuk K M, Hafner M, Renwick N, Tuschl T, Wernet P. BMC Genomics, 2013, 14:111.
[53] Zhang Y, Wang Z, Gemeinhart R A. J. Control. Release, 2013, 172:962.
[54] Wang H, Jiang Y, Peng H, Chen Y, Zhu P, Huang Y. Adv. Drug Deliver. Rev., 2015, 81:142.
[55] Ben-Shushan D, Markovsky E, Gibori H, Tiram G, Scomparin A, Satchi-Fainaro R. Drug Deliver. Transl. Res., 2014, 4:38.
[56] Muthiah M, Park I K, Cho C S. Expert Opin. Drug Delier., 2013, 10:1259.
[57] Liu X Q, Song W J, Sun T M, Zhang P Z, Wang J. Mol. Pharm., 2011, 8:250.
[58] Chen L, Charrier A, Zhou Y, Chen R, Yu B, Agarwal K, Tsukamoto H, Lee L J, Paulaitis M E, Brigstock D R. Hepatology, 2014, 59:1118.
[59] Zhang Y, Liu D, Chen X, Li J, Li L, Bian Z, Sun F, Lu J, Yin Y, Cai X, Sun Q, Wang K, Ba Y, Wang Q, Wang D, Yang J, Liu P, Xu T, Yan Q, Zhang J, Zen K,Zhang C Y. Mol. Cell, 2010, 39:133.
[60] Momen-Heravi F, Bala S, Bukong T, Szabo G. Nanomed. Nanotechnol., 2014, 10:1517.
[61] Munoz J L, Bliss S A, Greco S J, Ramkissoon S H, Ligon K L, Rameshwar P. Mol. Ther. Nucleic Acids, 2013, 2:e126.
[62] Dubois L G, Campanati L, Righy C, D'Andrea-Meira I, Spohr T C L S, Porto-Carreiro I, Pereira C M, Balça-Silva J, Kahn S A, DosSantos M F, Oliveira M A R, Ximenes-da-Silva A, Lopes M C, Faveret E, Gasparetto E L, Moura-Neto V. Front. Cell. Neurosci., 2014, 8:418.
[63] Yang J, Wei F, Schafer C, Wong D T W. PLoS ONE, 2014, 9:e0110641.
[64] Canitano A, Venturi G, Borghi M, Ammendolia M G, Fais S. Cancer Lett., 2013, 337:193.
[65] Le Garrec D, Ranger M, Leroux J C. Am. J. Drug Deliver., 2004, 2:15.
[66] Deng C, Jiang Y, Cheng R, Meng F, Zhong Z, Nano Today, 2012, 7:467.
[67] Kim C K, Lim S J. Arch. Pharm. Res., 2002, 25:229.
[68] Wang X, Guo Z. Chem. Soc. Rev., 2013, 42:202.
[69] Escudier B, Dorval T, Chaput N, André F, Caby M P, Novault S, Flament C,Leboulaire C, Borg C, Amigorena S, Boccaccio C, Bonnerot C, Dhellin O, Movassagh M, Piperno S, Robert C, Serra V, Valente N, Le Pecq J B, Spatz A, Lantz O, Tursz T, Angevin E, Zitvogel L. J. Transl. Med., 2005, 3:10.
[70] Morse M A, Garst J, Osada T, Khan S, Hobeika A, Clay T M, Valente N, Shreeniwas R, Sutton M A, Delcayre A, Hsu D H, Le Pecq J B, Lyerly H K. J. Transl. Med., 2005, 3:9.
[71] Anand P, Kunnumakkara A B, Newman R A, Aggarwal B B. Mol. Pharm., 2007, 4:807.
[72] Sharma R A, Gescher A J, Steward W P. Eur. J. Cancer, 2005, 41:1955.
[73] Hatcher H, Planalp R, Cho J, Torti F M, Torti S V. Cell. Mol. Life Sci., 2008, 65:1631.
[74] Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell R C, Ju S b, Mu J, Zhang L, Steinman L, Miller D, Zhang H G. Mol. Ther., 2011, 19:1769.
[75] Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee R K. Curr. Sci. India, 2004, 87:44.
[76] Chen W, Wang J, Shao C, Liu S, Yu Y, Wang Q, Cao X. Eur. J. Immunol., 2006, 36:1598.
[77] Eloy J O, Claro de Souza M, Petrilli R, Barcellos J P A, Lee R J, Marchetti J M. Colloid. Surface. B, 2014, 123:345
[78] Kataoka K, Harada A, Nagasaki Y. Adv. Drug Deliver. Rev., 2001, 47:113.
[79] Allen T M, Cullis P R. Science, 2004, 303:1818.
[80] Wang H, Xu, F, Li D, Liu X, Jin Q, Ji J. Polym. Chem. UK, 2013, 4:2004.
[81] Salvage J P, Thom C, Lewis A L, Phillips G J, Lloyd A W. J. Mater. Sci. Mater. Med., 2015, 26:14.
[82] Peer D, Karp J M, Hong S, Farokhzad O C, Margalit R, Langer R. Nat. Nanotechnol., 2007, 2:251.
[83] 刘儒涛(Liu R T),王世伟(Wang S W),刘晶(Liu J). 生物化学与生物物理进展(Prog. Biochem. Biophys),2013, 40(8):719.
[84] Jang S C, Gho Y S. Nanomedicine, 2014, 9:177.