构建纳米药物递送系统改善药物的理化性质和生物学性质已经成为现代药物设计研究的热点和重要方向。其中，多肽作为新兴的纳米药物的构筑基元具有良好生物相容性、自组装性与化学可变性等性质，激起了广泛的研究兴趣，为构建新型纳米递送系统提供了崭新的研究方向。本文阐述了自组装多肽在疏水作用、氢键、静电作用、π-π堆积等非共价作用力的综合作用下构建胶束、囊泡、球、纤维等不同形貌的纳米材料；进一步介绍了多肽药物结合物的基本概念以及高载药量、高生物利用度的优势，总结了近年来基于功能性多肽构建纳米药物递送系统的研究；重点介绍了近五年来报道的具有自组装性、增强溶解性、长效性、靶向性、刺激响应性、细胞跨膜性等多种功能的智能多肽纳米药物递送系统。
Nanomaterials for drug delivery have become a hot issue in the field of modern medicine since the successful improvement of the physicochemical and biological properties to drugs. Among them, peptides, as an emerging class of building block for nanomedicine, have attracted an extensive research interest due to their excellent properties such as good biocompatibility, easy self-assembly and chemical diversities, which point out a new direction for researchers to construct the novel and intelligent drug delivery systems. Herein, we report that the self-assembly peptides are driven by the integrated roles of noncovalent forces, including hydrophobic interaction, hydrogen bonding, electrostatic interaction and π-π stacking, to form a variety of well-defined nanostructures, such as micelles, vesicles, nanospheres, nanofibers, nanotube, disc and so on. Furtherly, the basic concept of peptide drug conjugates (PDCs) and their advantages of high drug loading, high bioavailability and specific targeting are introduced. The research in recent years on the construction of PDCs nanomedicine for drug delivery based on the functional peptide is summarized. We mainly focus on the most recent five-year report to construct the smart drug delivery system with the multifunction involved in self-assembly, enhancing solubility, long-term acting, targeting, stimulating response and cell transmembrane function.
Contents
1 Introduction
2 Self-assembling peptides
2.1 Classification of self-assembling peptides
2.2 The driving force of peptide assembly
3 Peptide drug conjugate for drug delivery system
3.1 Self-assembling peptide drug conjugates
3.2 Long-term acting peptide-drug conjugates
3.3 Targeting peptide drug conjugates
3.4 Responsive polypeptide drug conjugates
3.5 Transmembrane polypeptide drug conjugates
4 Conclusion
[1] Türeli N G, Türeli A E, Schneider M. Int. J. Pharm., 2016, 515(1/2):343.
[2] Atak B H, Buyuk B, Huysal M, Isik S, Senel M, Metzger W, Cetin G. Carbohydr. Polym., 2017, 164:200.
[3] Yao Q Q, Cosme J G, Xu T, Miszuk J M, Picciani P H, Fong H, Sun H L. Biomaterials, 2017, 115:115.
[4] Deodhar G V, Adams M L, Joardar S, Joglekar M, Davidson M, Mettler M, Toler S A, Davies F, Trewyn B G. Langmuir, 2017, 34(1):228.
[5] Wu W, Jiang C Z, Roy V A. Nanoscale, 2016, 8(47):19421.
[6] Ghadiri M R, Granja J R, Milligan R A, Mcree D E, Khazanovich N. Nat., 1993, 366(6453):324.
[7] Zhang S, Holmes T, Lockshin C, Rich A. Proc. Natl. Acad. Sci., 1993, 90(8):3334.
[8] Chen Z P, Xing L, Fan Q, Cheetham A G, Lin R, Holt B, Chen L W, Xiao Y Y, Cui H G. Theranostics, 2017, 7(7):2003.
[9] Smith D J, Brat G A, Medina S H, Tong D, Yong H, Grahammer J, Furtmüller G J, Oh B C, Nagysmith K J, Walczak P. Nat. Nanotechnol., 2016, 11(1):95.
[10] Dehsorkhi A, Castelletto V, Hamley I W. J. Pept. Sci., 2014, 20(7):453.
[11] Hu X X, He P P, Qi G B, Gao Y J, Lin Y X, Chao Y, Yang P P, Hao H, Lei W, Hao W. ACS Nano, 2017, 11(4):4086.
[12] Ardoña H A M, Tovar J D. Chem. Sci., 2015, 6(2):1474.
[13] Groot N S D, Parella T, Aviles F X, Vendrell J, Ventura S. Biophys. J., 2007, 92(5):1732.
[14] Mandal D, Nasrolahi S A, Parang K. Org. Biomol. Chem., 2014, 12(22):3544.
[15] Deshmukh S A, Solomon L A, Kamath G, Fry H C. Nat. Com., 2016, 7:12367.
[16] Yu T, Lee O S, Schatz G C. J. Phys. Chem. A, 2013, 117(32):7453.
[17] Grajda M, Lewińska M J, Szumna A. Org. Biomol. Chem., 2017, 15(40):8513.
[18] Hamley I W. Soft Matter, 2011, 7(20):9533.
[19] Aulisa L, Dong H, Hartgerink J D. Biomacromolecules, 2009, 10(9):2694.
[20] Trent A, Marullo R, Lin B, Black M, Tirrell M. Soft Matter, 2011, 7(20):9572.
[21] Zhu X M, Zou R F, Sun P, Wang Q, Wu J C. Polym. Chem., 2018, 9:69.
[22] Niece K L, Hartgerink J D, Donners J J, Stupp S I. J. Am. Chem. Soc., 2003, 125(24):7146.
[23] Ramachandran S, Tseng Y, Yu Y B. Biomacromolecules, 2005, 6(3):1316.
[24] Behanna H A, Donners J J, Gordon A C, Stupp S I. J. Am. Chem. Soc., 2005, 127(4):1193.
[25] Tsonchev S, And G C S, Ratner M A. J. Phys. Chem. B, 2015, 108(26):8817.
[26] Tao K, Levin A, Adler-Abramovich L, Gazit E. Chem. Soc. Rev., 2016, 45(14):3935.
[27] Bushuyev O S, Peterson G R, Brown P, Maiti A, Gee R H, Weeks B L, Hope-Weeks L J. Chemistry, 2013, 19(5):1706.
[28] Luo J H, Graslund A, Abrahams J P. J. Biol. Chem., 2017, 292(5):2046.
[29] Bowerman C J, Liyanage W, Federation A J, Nilsson B L. Biomacromolecules, 2011, 12(7):2735.
[30] Bertness K A, Sanders A W, Rourke D M, Harvey T E, Roshko A, Schlager J B, Sanford N A. Adv. Funct. Mater., 2010, 20(17):2911.
[31] Yin W, Cheetham A G, Angacian G, Hao S, Xie L S, Cui H G. Adv. Drug Delivery Rev., 2016,:110.
[32] Fung S Y, Yang H, Sadatmousavi P, Sheng Y, Mamo T, Nazarian R, Chen P. Adv. Funct. Mater., 2011, 21(13):2456.
[33] Webber M J, Newcomb C J, Bitton R, Stupp S I. Soft Matter, 2011, 7(20):9665.
[34] Wang Q R, Zhang X, Zheng J H, Liu D J. RSC Adv., 2014, 4(48):25461.
[35] Li J Y, Kuang Y, Gao Y, Du X, Shi J F, Xu B. J. Am. Chem. Soc., 2013, 135(2):542.
[36] Fatouros D, Lamprou D A, Urquhart A J, Yannopoulos S N, Vizirianakis I S, Zhang S, Koutsopoulos S. ACS Appl. Mater., 2014, 6(11):8184.
[37] Rodríguezvázquez N, Amorín M, Granja J R. Org. Biomol. Chem., 2017, 15(21):4490.
[38] Panda J J, Mishra A, Basu A, Chauhan V S. Biomacromolecules, 2008, 9(8):2244.
[39] Yan C Q, Pochan D J. Cheminform, 2010, 39(9):3528.
[40] Panda J J,Yandrapu S,Kadam R S,Chauhan V S,Kompella U B. J. Control Release, 2013, 172(3):1151.
[41] Jin H L, Zhao G F, Hu J L, Ren Q G, Yang K, Wan C, Huang A, Li P D, Feng J P, >ñ J W. ACS Appl. Mater., 2017, 9(31):25755.
[42] Castelletto V, Cheng G, Stain C, Connon C J, Hamley I W. Langmuir, 2012, 28(31):11599.
[43] Tajima A, Liu W, Pradhan I, Bertera S, Lakomy R, Rudert W A, Trucco M, Meng W S, Fan Y. J. Vis. Exp., 2016,6(112):54062.
[44] Mazza M, Notman R, Anwar J, Rodger A, Hicks M, Parkinson G, Mccarthy D, Daviter T, Moger J, Garrett N. ACS Nano, 2013, 7(2):1016.
[45] Lindsey S, Piatt J H, Worthington P, Sönmez C, Satheye S, Schneider J P, Pochan D J, Langhans S A. Biomacromolecules, 2015, 16(9):2672.
[46] Xu X D, Liang L, Chen C S, Lu B, Wang N L, Jiang F G, Zhang X Z, Zhuo R X. ACS Appl. Mater., 2010, 2(9):2663.
[47] Webber M J, Matson J B, Tamboli V K, Stupp S I. Biomaterials, 2012, 33(28):6823.
[48] Soukasene S, Toft D J, Moyer T J, Lu H, Lee H K, Standley S M, Cryns V L, Stupp S I. ACS Nano, 2011, 5(11):9113.
[49] Wang Q R, Zhang X, Zheng J H, Liu D J. RSC Adv., 2014, 4:25461.
[50] Li X M, Li J Y, Gao Y, Kuang Y, Shi J F, Xu B. J. Am. Chem.Soc., 2010, 132:17707.
[51] Wang M, Cheetham A G, Cui H G. Nano Today, 2016, 11(1):13.
[52] Lindgren M, Rosenthal-Aizman K, Saar K, Eiríksdóttir E, Jiang Y, Sassian M, Ostlund P, Hallbrink M, Langel U. Biochem. Pharmacol., 2006, 71(4):416.
[53] He X, Na M H, Kim J S, Lee G Y, Park J Y, Hoffman A S, Nam J O, Han S E, Sim G Y, Oh Y K. Mol. Pharmaceutics., 2011, 8(2):430.
[54] Yu-Yin L E, Huang L J, Jun-Yan H E. J. Chinese Oncology, 2017, 23(6):502.
[55] Meng S Y, Su B, Li W, Ding Y M, Tang L, Zhou W, Song Y, Li H Y, Zhou C C. Nanotechnology, 2010, 21(41):415103.
[56] Mayr J, Hager S, Koblmüller B, Klose M H M, Holste K, Fischer B, Pelivan K, Berger W, Heffeter P, Kowol C R. J. Biol. Inorg. Chem., 2017, 22(4):591.
[57] Khodadust F, Ahmadpour S, Aligholikhamseh N, Abedi S M, Hosseinimehr S J. Eur. J. Med. Chem., 2017, 144:767.
[58] Dobroff A S, Eckhardt B L, Salmeron C C, Cimino D F, Arap W, Pasqualini R. Cancer Res., 2015, 75(15 Supplement):3543.
[59] Mokhtarzadeh A, Parhiz H, Hashemi M, Ayatollahi S, Abnous K, Ramezani M. AAPS PharmSciTech., 2015, 16(5):1025.
[60] Yao H R, Veine D M, Livant D L. Breast Cancer Res. Treat., 2016, 157(3):1.
[61] Milosavljevic V, Krejcova L, Guran R, Buchtelova H, Wawrzak D, Richtera L, Heger Z, Kopel P, Adam V. Colloid Surface B, 2017, 156:123.
[62] Ghosh A, Raju N, Tweedle M, Kumar K. Cancer Biother Radiopharm, 2017, 32(1):24.
[63] Xiao W J, Chen X, Yang L, Mao Y Q, Wei Y Q, Chen L J. Int. J. Pharm., 2010, 393(1/2):120.
[64] Katanasaka Y, Ishii T, Asai T, Naitou H, Maeda N, Koizumi F, Miyagawa S, Ohashi N. Int. J. Cancer., 2010, 127(11):2685.
[65] Rivera-Fillat M P, Reig F, Martínez E M, Grau-Oliete M R. J. Pept. Sci., 2010, 16(7):315.
[66] He S, Cen B H, Liao L M, Wang Z, Qin Y X, Wu Z M, Liao W J, Zhang Z Y, Ji A M. Drug Deliv., 2017, 24(1):471.
[67] Nishimura Y, Takeda K, Ezawa R, Ishii J, Ogino C, Kondo A. J. Nanobiotechnology, 2014, 12(1):11.
[68] Zhu L, Wang T, Perche F, Taigind A, Torchilin V P. PNAS, 2013, 110(42):17047.
[69] Zhu L, Perche F, Wang T, Torchilin V P. Biomaterials, 2014, 35(13):4213.
[70] Tu Y, Lin Z. J. Control Release., 2015, 212:94.
[71] He B, Ma S Y, Peng G F, He D H. Nanomedicine, 2017, 14(2):365.
[72] Rizzuti M, Nizzardo M, Zanetta C, Ramirez A, Corti S. Drug Discov. Today, 2015, 20(1):76.
[73] Ablan F O, Spaller B L, Abdo K, Almeida P. Biophys J., 2016, 111(8):1738.
[74] Vasconcelos L, Madani F, Arukuusk P, Parnaste L, Graslund A, Langel U. Biochim Biophys Acta, 2014, 1838(12):3118.
[75] Bolhassani A, Jafarzade B S, Mardani G. Peptides, 2017, 87:50.
[76] Xue G Q, Liu Z, Wang L X, Zu L. J. Mass Spectrom., 2015, 50(1):220.
[77] Jones S, Howl J. Methods Mol Biol., 2011, 683(4):291.
[78] Duan Z Q, Chen C, Qin J, Liu Q, Wang Q, Xu X C, Wang J X. Drug Deliv., 2017, 24(1):752.
PDF
(2728KB)
