动脉粥样硬化和血栓的一个主要症状为血管病变引起的血管狭窄。动脉粥样硬化能够引发心肌梗塞和脑梗塞等疾病，严重威胁人类生命健康。因此，发展治疗血管狭窄疾病的有效方法至关重要。动脉血管的严重狭窄造成其血管壁剪切应力比健康血管至少增大一个数量级，这种显著区别的剪切应力可以用来作为药物靶向传递的触发信号。剪切响应性药物传递体系能够在增大的剪切应力下在血管狭窄部位释放负载的药物，从而起到靶向治疗的效果，且对于正常组织和器官的副作用很小，对于治疗动脉粥样硬化及血管局部栓塞等血管狭窄疾病具有非常重要的意义，因此这种新的刺激响应性药物传递体系正成为领域内的研究热点。本文综述了剪切响应性药物传递体系的最新研究进展，分类介绍了这些剪切响应性药物载体的设计思路和作用机制，并对当前剪切响应性药物传递体系面临的困难和存在的不足进行了讨论，对其发展前景作了展望。
One major symptom of atherosclerosis and vascular thrombosis is vascular stenosis caused by vascular lesion. Atherosclerosis has become one of the major threats to human health since it can result in severe diseases such as myocardial infarction and cerebral infarction. Therefore,it is of great significance to develop more effective ways to treat vascular stenosis diseases. The wall shear stress at severely stenosed arteries is at least one order of magnitude higher than that in healthy vessels. The significantly increased mechanical force could be used as a trigger signal for effective targeted drug delivery. Shear-responsive drug delivery systems can release their payloads under increased shear stress at the stenosed sites and have minimal side effects on the normal tissues and organs. Therefore, this natural physical trigger is an important and promising approach for targeted drug delivery to cure some cardiovascular diseases, especially vascular stenosis diseases such as atherosclerosis. Shear-responsive drug delivery systems have attracted great interests of researchers. The recent advances on shear-responsive drug delivery systems are reviewed. Various shear-responsive drug delivery systems classified on the basis of design ideas and responsive mechanisms are discussed. At last, the urgent needs, challenges and some personal perspectives of the shear-responsive drug carriers are also presented.
Contents
1 Introduction
2 Mechanism of shear-responsive drug delivery
3 Shear-responsive drug delivery systems
3.1 Aggregates of nanoparticles
3.2 Microcapsules and vesicles
3.3 RBCs-nanoparticles composite carriers
3.4 Supramolecular self-assembly hydrogels
4 Conclusion
[1] Ingall T J, O'Fallon W N, Asplund K, Goldfrank L R, Hertzberg V S, Louis T A, Christianson T G H. Stroke, 2004, 35:2418.
[2] Wechsler L R. New Engl. J.Med., 2011, 364:2138.
[3] Bark D L, Ku D N. J Biomech., 2010, 43:2970.
[4] Foin N, Lee R D, Torii R, Guitierrez-Chico J L, Mattesini A, Nijjer S, Sen S Y, Petraco R, Davies J E, Mario C D, Joner M, Virmani R, Wong P. Int. J. Cardiol., 2014, 177:800.
[5] Coskunm M, Vermeire S, Nielsen O H. Trends Pharmacol. Sci., 2017, 38:127.
[6] Ulbrich K, Hola K, Subr V, Bakandritsos A, Tucek J, Zboril R. Chem. Rev., 2016, 116:5338.
[7] Tibbitt M W, Dahlman J E, Langer R. J. Am. Chem. Soc., 2016, 138:704.
[8] Maeda H, Matsumura Y. Adv. Drug Deliver. Rev., 2011, 63:129.
[9] Fang J, Nakamura H, Maeda H. Adv. Drug Deliver. Rev., 2011, 63:136.
[10] Jiang K, Chi T, Li T, Zheng G R, Fan L L, Liu Y J, Chen X F, Chen S J, Jia L, Shao J W. Nanoscale, 2017, 9:9428.
[11] Zheng H Q, Zhang Y N, Liu L F, Wan W, Guo P, Nystrom A M, Zou X D. J. Am. Chem. Soc., 2016, 138:962.
[12] Baek S, Singh R K, Kim T H, Seo J, Shin U S, Chrzanowski W, Kim H W. ACS Appl. Mater. Inter., 2016, 8:8967.
[13] Wang X Y, Zhang J S, Wang Y T, Wang C P, Xiao J R, Zhang Q, Cheng Y Y. Biomaterials, 2016, 81:114.
[14] Wang Z P, Feng Z Q, Gao C Y. Chem. Mater., 2008, 20, 4194.
[15] Sutton J T, Haworth K J, Pyne-Geithman G, Holland C K. Expert Opin. Drug Deliv., 2013, 10:573.
[16] Wang G S, Ma Y Y, Wei Z Y, Qi M. Chem. Eng. J., 2016, 289:150.
[17] Nieuwlaat R, Schwalm J D, Khatib R, Yusuf S. Eur. Heart J, 2013, 34:1262.
[18] Cicha I, Singh R, Garlichs C D, Alexiou C. J. Control. Release, 2016, 229:23.
[19] Saxer T, Zumbuehl A, Mueller B. Cardiovasc. Res., 2013, 99:328.
[20] Lowe G D. Baillieres Best Pract. Res. Clin. Haematol.,1999, 12, 435.
[21] Cunningham K S, Gotlieb A I. Lab. Invest., 2005, 85:9.
[22] Ernst W, Jan O, Ulrich K. Atherosclerosis, 2011, 216:277.
[23] Nesbitt W S, Westein E, Tovar-Lopez F J, Tolouei E, Mitchell A, Fu J, Carberry J, Fouras A, Jackson S P. Nat. Med., 2009, 15:665.
[24] Fisher A B, Chien S, Barakat A L, Nerem R M. Am. J. Physiol. Lung Cell Mol. Physiol., 2001, 281:1529.
[25] Wootton D M, Ku D N. Annu. Rev. Biomed. Eng., 1999, 1:299.
[26] Bark D L, Ku D N. J. Biomech., 2010, 43:2970.
[27] Jo Y S, Vlies A J, Gantz J, Thacher T, Antonijevic S, Cavadini S, Demurtas D, Stergiopulos N, Hubbell J A. J. Am. Chem. Soc., 2009, 131:14413.
[28] Holme M N, Fedotenko I A, Abegg D, Althaus J, Babel L, Favarger F, Reiter R, Tanasescu R, Zaffalon P L, ZieglerA, Müller B, Saxer T, Zumbuehl A. Nat. Nanotechnol., 2012, 7:536.
[29] Korin N, Kanapathipillai M, Matthews M D, Crescente M, Brill A, Mammoto T, Ghosh K, Jurek S, Bencherif S A, Bhatta D, Coskun A U, Feldman C L, Wagner D D, Ingber D E. Science, 2012, 337:738.
[30] Marosfoi M G, Korin N, Gounis M J, Uzun O, Vedantham S, Langan E T, Papa A L, Brooks O W, Johnson C, Puri A S, Bhatta D, Kanapathipillai M, Bronstein B R, Chueh J Y, Ingber D E, Wakhloo A K. Stroke, 2015, 46:3507.
[31] Mellal L, Belharet K, Folio D, Ferreira A. Nanopart. Res., 2015, 17:64.
[32] Zanina A, Vilesov A, Budtova T. Int. J. Pharm., 2002, 242:137.
[33] Zeo U, Tarabukina E, Budtova T. J. Controlled Release, 2005, 108:73.
[34] Tong W J, Song X X, Gao C Y. Chem. Soc. Rev., 2012, 41:6103.
[35] 仝维鋆(Tong W J), 高长有(Gao C Y). 高等学校化学学报(Chemical Journal of Chinese Universities),2008, 29(7):1285.
[36] She S P, Xu C X, Yin X F, Tong W J, Gao C Y. Langmuir, 2012, 28:5010.
[37] She S P, Li Q Q, Shan B W, Tong W J, Gao C Y. Adv. Mater., 2013, 25:5814.
[38] Natsume T, Yoshimoto M. ACS Appl. Mater. Inter., 2014, 6:3671.
[39] Staedtke V, Brahler M, Muller A, Georgieva R, Bauer S, Sternberg N, Voigt A, Lemke A, Keck C, Moschwitzer J, Baumler H, Small, 2010, 6:96.
[40] Muzykantov V R, Sakharov D V, Smirnov M D, Domogatsky S P, Samokhin G P. FEBS Lett., 1985, 182:62.
[41] Muzykantov V R. Exper. Opin. Drug Delivery, 2010, 7:403.
[42] Azarmi S, Roa W H, Lobenberg R. Adv. Drug Delivery Rev., 2008, 60:863.
[43] Faraji A H, Wipf P. Bioorg. Med. Chem., 2009, 17:2950.
[44] Wang A Z, Langer R, Farokhzad O C. Annu. Rev. Med., 2012, 63:185.
[45] Anselmo A C, Kumar S, Gupta V, Pearce A M, Ragusa A, Muzykantov V, Mitragotri S. Biomaterials, 2015, 68:1.
[46] Zhao Y N, Sun X X, Zhang G N, Trewyn B G, Slowing I I, Lin V S Y. ACS Nano, 2011, 5:1366.
[47] Anselmo A C, Gupta V, Zern B J, Pan D, Zakrewsky M, Muzykantov V, Mitragotri S. ACS Nano, 2013, 7:11129.
[48] Chambers E, Mitragotri S. J. Controlled Release, 2004, 100:111.
[49] Chambers E, Mitragotri S. Exp. Biol. Med., 2007, 232:958.
[50] Chen C J, Li S K, Liu K, Ma G H, Yan X H. Small, 2016, 12:4719.
[51] Kaplan J A, Barthélémy P, Grinstaff M W. Chem. Commun., 2016, 52:5860.
[52] Himmelein S, Lewe V, Stuartb M C A, Ravoo B J. Chem. Sci., 2014, 5:1054.
[53] Feng Q, Wei K C, Lin S, Xu Z, Sun Y X, Shi P, Li G, Bian L M. Biomaterials, 2016, 101:217.
[54] Rodell C B, Kaminski A L, Burdick J A. Biomacromolecules, 2013, 14:4125.
[55] Jia Y G, Zhu X X. Chem. Mater., 2015, 27:387.
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