Abstract: MicroRNA (miRNA) is a class of small regulatory noncoding RNA (approximately 21—25 bases) endogenously expressed in animals, plants and pathogenic microorganisms. It has the function at the translation level as an important gene expression regulator. Until now, more than 1 000 miRNAs have been identified in organisms, which could regulate around 30% of human genes. MiRNA also plays a key role in cell growth, differentiation and apoptosis. More importantly, studies demonstrate that the expression of miRNAs in organisms is tightly associated with neurological disorders, cardiovascular diseases, cancer and viral infections. Therefore, miRNA has been widely used for early diagnosis, prognostic evaluation and therapeutic targets of many diseases. Regulating expression of miRNA by RNA interference technology in organisms has attracted more and more attention. By delivering miRNA or “antisense” nucleotides to cells, the expression level of target miRNA can be regulated, so as to achieve the treatment of diseases caused by gene disorders. Currently, miRNA-based therapeutics have shown great potential in cancer, emerging infectious diseases and other diseases. However, the characteristics of nucleotide chains, such as negativity and degradability, make it difficult for nucleotide chains to cross cell membranes into cells. Therefore, the rational design of delivery vectors is of great significance for improving the delivery and efficiency of therapeutic genes. Until now, it has been reported that a variety of materials can be used as gene carriers for intracellular delivery of miRNA. Liposome capsules can enter the cell through endocytosis, which are prepared by encapsulating drug molecules in vesicles formed by phospholipid bilayer membranes. In addition, using the physical and chemical properties of different materials, various forms of nanocarriers, such as polymer nanoparticles, organic and inorganic nanoparticles, have been successfully developed and designed, which can achieve targeted delivery of gene drugs and intelligent stimulus release. In this review, we will discuss the function of intracellular miRNA and the methods of regulating the expression of miRNA, summarize the progress of nanocarriers in delivering miRNA therapeutic genes, and analyze the design ideas, methods and mechanisms of nanocarriers systems. In addition, according to the current research progress, we will discuss the development direction of miRNA-based therapy in emerging areas, in order to provide reference for the preparation of new intelligent gene delivery system.
Griffithss J S. Nucleic Acids Research,2004,32,D109.2 Calin G A, Croce C M. Nature Reviews Cancer,2006,6(11),857.3 Chi S W, Zang J B, Mele A, et al. Nature,2009,460(7254),479.4 Lee R C, Feinbaum R L, Ambros V. Cell,1993,75(5),843.5 Yu F, Yao H, Zhu P, et al. Cell,2007,131(6),1109.6 Pauli A, Rinn J L, Schier A F. Nature Reviews Genetics,2011,12(2),136.7 Li C, Feng Y, Coukos G, et al. Advances in Applied & Pharmaceutical Sciences Journal,2009,11(4),747.8 Petrocca F, Lieberman J. Advances in Immunology,2009,102(102),227.9 O’Connell R M, Rao D S, Chaudhuri A A, et al. Nature Reviews Immunology,2010,10(2),111. 10 Yin J Q, Zhao R C, Morris K V. Trends in Biotechnology,2008,26(2),70.11 Iorio M V, Ferracin M, Liu C G, et al. Cancer Research,2005,65(16),7065.12 Ryan B M, Robles A I, Harris C C.Nature Reviews Cancer,2010,10(6),389.13 Taka K, Kataoka K.European Journal of Pharmaceutics and Biopharmaceutics,2009,71(3),475.14 Yang C H, Zhang M Z, Merlin D. Journal of Materials Chemistry B,2018,6,1312.15 Zhi D F, Bai Y C, Yang J, et al. Advances in Colloid and Interface Scie-nce,2018,253,117.16 Yu B, Ouyang C, Qiu K, et al. Chemistry,2015,21(9),3691.17 Zhao Y N, Qureshi F, Zhang S B, et al. Journal of Materials Chemistry B,2014,2(19),2920.18 Zhi D, Zhang S, Cui S, et al. Bioconjugate Chemistry,2013,24(4),487.19 Srinivas R, Samanta S, Chaudhuri A. Chemical Society Review,2009,38(12),3326.20 Sato Y, Hatakeyama H, Sakurai Y, et al. Journal of Controlled Release,2012,163(3),267.21 Love K T, Mahon K P, Levins C G, et al. Proceedings of the National Academy of Sciences of the United States of America,2010,107(5),1864.22 Pecot C V, Calin G A, Coleman R L, et al. Nature Reviews Cancer,2011,11(1),59.23 Lin X, Li L, Wang R, et al. RNA,2011,17(4),603.24 Zhdanova R I, Podobeda O V, Vlassov V V. Bioelectrochemistry,2002,58(1),53.25 Wu Y, Crawford M, Yu B, et al. Molecular Pharmaceutics,2011,8(4),1381.26 Pramanik D, Campbell N R, Karikari C, et al. Molecular Cancer Therapy,2011,10(8),1470.27 Piao L Z, Zhang M C, Datta J, et al. Molecular Therapy,2012,20(6),1261.28 Hus S H, Yu B, Wang X M, et al. Nanomed Nanotechnol,2013,9(8),1169.29 Koltover I, Salditt T, Rädler J O, et al. Science,1998,281(5373),78.30 Balazs D A, Godbey W T.Journal of Drug Delivery,2011,32(1),6497.31 Wang X M, Yu B, Ren W, et al. Journal of Controlled Release,2013,172(3),690.32 Liu J W, Meng T T, Yuan M, et al. International Journal of Nanomedicine,2016,11,6713.33 Shi J S, Zhong Z R, Liu J, et al. Pharmaceutical Research,2012,29(1),97.34 Botto C, Mauro N, Amore E, et al. International Journal of Pharmaceutics,2017,516(1-2),334.35 Shi S J, Han L, Gong T, et al. Angewandte Chemie-International Edition,2013,52(14),3901.36 Shi S J, Han L, Deng L, et al. Journal of Controlled Release,2014,194,228.37 Lv H T, Zhang S B, Wang B, et al. Journal of Controlled Release,2006,114(1),100.38 Shi J, Yu S, Zhu J, et al. Colloids Surf B: Biointerfaces,2016,141,417.39 Karimi M, Ghasemi A, Sahandi Zangabad P, et al. Chemical Society Reviews,2016,45(5),1457.40 Ulbrich K, Hola K, Subr V, et al. Chemical Reviews,2016,116(9),5338.41 Movahedi F, Hu R G, Becker D L, et al. Nanomed-Nanotechnol,2015,11(6),1575.42 Zhi D, Zhang S, Wang B, et al. Bioconjugate Chemistry,2010,21(4),563.43 Puras G, Mashal M, Zarate J, et al. Journal of Controlled Release,2014,174(2),27.44 Chen Y C, Zhu X D, Zhang X J, et al. Molecular Therapy,2010,18(9),1650.45 Liu X Q, Song W J, Sun T M, et al. Molecular Pharmaceutics,2011,8(1),250.46 Wiggins J F, Ruffino L, Kelnar K, et al. Cancer Research,2010,70(14),5923.47 Trang P, Wiggins J F, Daige C L, et al. Molecular Therapy,2011,19(6),1116.48 Cardlik R, Celec P, Bernadic M, et al. Bratislavské Lekárske Listy,2011,112(8),428.49 Sun Q, Zhou Z, Qiu N, et al. Advanced Materials,2017,29(14),1606628.50 Mohamed N K, Hamad M A, Hafez M Z, et al. International Journal of Cancer,2017,140(7),1475.51 Li M, Zhang W, Wang B, et al. International Journal of Nanomedicine,2016,11,5645.52 Zhang X, Ng H L H, Lu A, et al. Nanomedicine,2016,12(4),853.53 Riviere K.Journal of Drug Targeting,2011,19(1),14.54 Yang X, Koh C G, Liu S, et al. Molecular Pharmaceutics,2009,6(1),221.55 Jiang J, Yang S J, Wang J C, et al. European Journal of Pharmaceutics and Biopharmaceutics,2010,76(2),170.56 Pan L, Liu J, He Q, et al. Advanced Materials,2014,26(39),6742.57 Ling D, Lee N, Hyeon T. Accounts of Chemical Research,2015,48(5),1276.58 Yuan P, Mao X, Chong K C, et al. Small,2017,13(27),1700569.59 Torchilin V P, Levchenko T S, Rammohan R, et al. Proceedings of the National Academy of Sciences of the United States of America,2003,100(4),1972.60 Zhang M Z, Zhou X, Wang B, et al. Journal of Controlled Release,2013,168(3),251.61 Liu M F, Li M H, Sun S, et al. Biomaterials,2014,35(11),3697.62 Liu J, Dang L, et al. Biomaterials,2015,52,148.63 Costa P M, Cardoso A L, Custodia C, et al. Journal of Controlled Release,2015,207,31.64 Suzuki R, Takizawa T, Negishib Y, et al. Journal of Controlled Release,2007,117(1),130.65 Negishi Y, Endo Y, Fukuyama T, et al. Journal of Controlled Release,2008,132(2),124.66 Negishi Y, Endo-Takahashi Y, Matsuki Y, et al. Molecular Pharmaceutic,2012,9(9),1834.67 Endo-Takahashi Y, Negishi Y, Nakamura A, et al. Scientific Reports,2014,4(1),3883.68 Boussif O, Lezoualc’h F, et al. Proceedings of the National Academy of Sciences of the United States of America,1995,92,7297.69 Ibrahim A F, Weirauch U, Thomas M, et al. Cancer Research,2011,71(15),5214.70 Morishita Y, Imai T, Yoshizawa H, et al. International Journal of Nanomedicine,2015,10,3475.71 Rytblat I, Wu N, Xu H L, et al. Nano Research,2016,9(6),1609.72 Wang S P, Zhang J M, Wang Y T, et al. Nanomedicine-Nanotechnology Biology and Medicine,2016,12(2),411.73 Wang Y D, Chen J W, Liang X, et al. Molecular Pharmaceutics,2017,14(7),2323.74 Hwang D W, Song S, Jang J, et al. Biomaterials,2011,32(21),4968.75 Chiou G Y, Cherng J Y, Hsu H S, et al. Journal of Controlled Release,2012,159(2),240.76 Chien Y, Chang Y L, Li H Y, et al. Acta Biomaterialia,2015,13,228.77 Gao S Q, Tian H, Guo Y, et al. Acta Biomaterialia,2015,25,184.78 Wang M, Guo Y, Yu M, et al. Acta Biomaterialia,2017,54,69.79 Zhu Y L, Liang G F, Sun B, et al. International Journal of Nanomedicine,2016,11,399.80 Li H M, Fu Y, Zhang T, et al. Advanced Functional Materials,2015,25(48),7457.81 Lü J M, Liang Z D, Wang X X, et al. Nanomedicine,2016,11(15),1971.82 Son S, Hwang D W, Singha K, et al. Journal of Controlled Release,2011,155(1),18.83 Hwang D W, Son S, Jang J, et al. Biomaterials,2011,32(21),4968.84 Zhang T T, Xue X, He D L, et al. Cancer Letters,2015,365(2),156.85 Li H M, Jiang H, Zhao M N, et al. Polymer Chemistry,2015,6,1952.86 Devulapally R, Paulmurugan R. Wiley Interdisciplinary Reviews-Nanome-dicine and Nanobiotechnology,2014,6(1),40.87 Moore L B, Sawyer A J, Saucier-Sawyer J, et al. Biomaterials,2016,89,127.88 Ananta J S, Paulmurugan R, Massoud T F. Molecular Pharmaceutics,2016,13(9),3164.89 Ananta J S, Paulmurugan R, Massoud T F. Molecular Pharmaceutics,2015,12(12),4509.90 Ramezani M, Ebrahimian M, Hashemi M. Current Medicinal Chemistry,2017,24(7),728.91 Devulapally R, Sekar N M, Sekar T V, et al. American Chemical Society Nano,2015,9(3),2290.92 Liang G, Zhu Y, Jing A, et al. Gene Therapy,2016,23(12),829.93 Ahmed N, Fessi H.Journal of Colloid Science and Biotechnology,2016,5(1),69.94 Zhou Y L, Zhang L, Zhao W, et al. Biomaterials,2013,34(33),8269.95 Cheng C J, Saltzman W M.Molecular Pharmaceutics,2012,9(5),1481.96 Patil Y, Panyam J.International Journal of Pharmaceutics,2009,367(1-2),195.97 Barichello J M, Morishita M, Takayama K, et al. Drug Development and Industrial Pharmacy,1999,25(4),471.98 Liang G F, Zhu Y L, Sun B, et al. Nanoscale Research Letters,2011,6(1),447.99 Arora S, Swaminathan S K, Kirtane A, et al. International Journal Nanomedicine,2014,9,2933.100 Bhargava-Shah A, Foygel K, Devulapally R, et al. Nanomedicine,2016,11(3),235.101 Devulapally R, Sekar T V, Paulmurugan R.Molecular Pharmaceutics,2015,12(6),2080.102 Devulapally R, Foygel K, Sekar T V, et al. American Chemistry Society Applied Materials Interfaces,2016,8(49),33412.103 Devulapally R, Sekar N M, Sekar T V, et al. American Chemical Society Nano,2015,9(3),2290.104 Wang T Y, Choe J W, Pu K Y, et al. Journal of Controlled Release,2015,203,99.105 Edwards D A, Hanes J, Caponetti G, et al. Science,1997,276(5320),1868.106 Kim T K, Yoon J J, Lee D S, et al. Biomaterials,2006,27(2),152.107 Kwon M J, Bae J H, Kim J J, et al. International Journal of Pharmaceutics,2007,333(1-2),5.108 Yang Y, Bajaj N, Xu P, et al. Biomaterials,2009,30(10),1947.109 Wang C H, Wu D, Yang J B, et al. Royal Society of Chemistr Advances,2015,5(99),81445.110 Wu D, Wang C H, Yang J B, et al. Molecular Pharmaceutics,2016,13(11),3925.111 Mao S R, Sun W, Kissel T. Advanced Drug Delivery Reviews,2010,62(1),12.112 Vauthier C, Zandanel C, Ramon A L. Current Opinion Colloid Interface Science,2013,18(5),406.113 Prashanth K V H, Tharanathan R N. Trends in Food Science Technology,2007,18(3),117.114 Gaur S, Wen Y F, Song J H, et al. Oncotarget,2015,6(30),29161.115 Wang Z, Wu G S, Wei M Y, et al. International Journal Nanomedicine,2016,11,2091.116 Santos-Carballal B, Aaldering L J, Ritzefeld M, et al. Scientific Reports,2015,5,13567. 117 Zhou F, Jia X L, Yang Q M, et al. Biomaterials Science,2016,4(5),849.118 Liu X, Rocchi P, Peng L. New Journal of Chemistry,2012,36(2),256.119 Ravina M, Paolicelli P, Seijo B, et al. Mini-Reviews in Medicinal Che-mistry,2010,10(1),73.120 Ren Y, Kang C S, Yuan X B, et al. Journal of Biomaterials Science,2010,21(3),303.121 Han H B, Yang J B, Wang Y D, et al. Biomaterials Science,2017,5(11),2268.122 Wang H M, Zhao X, Guo C H, et al. Plos One,2015,10(9),0139136.123 Chen W Q, Liu Y, Liang X, et al. Acta Biomaterialia,2017,57,238.124 Xue H Y, Liu Y, Liao J Z, et al. Oncotarget,2016,7(52),86675.125 Zhang D, Xiao M, Ma X, et al. Materials Review B:Research Papers,2017,31(1),25(in Chinese).张栋, 肖淼, 马迅, 等.材料导报:研究篇,2017,31(1),25.126 Pan T, Song W J, Gao H C, et al. American Chemistry Society Applied Materials Interfaces,2016,8(30),19217.127 Ekin A, Karatas O F, Culha M, et al. Journal of Gene Medicine,2014,16,331.128 Ghosh R, Singh L C, Shohet J M, et al. Biomaterials,2013,34(3),807.129 Huang S N, Duan S F, Wang J, et al. Advanced Functional Materials,2016,26(15),2532.130 Kang L, Hu P, Yang J, et al. Materials Review A:Review Papers,2015,29(11),132(in Chinese).康路,胡平,杨军,等.材料导报:综述篇,2015,29(11),132.131 Viola K L, Sbarboro J, Sureka R, et al. Nature Nanotechnology,2015,10(1),91.132 Zanganeh S, Hutter G, Spitler R, et al. Nature Nanotechnology,2016,11(11),986.133 Long M J C, Pan Y, Lin H C, et al. Journal of the American Chemical Society,2011,133(26),10006.134 Kim B H, Lee N, Kim H, et al. Journal of the American Chemical Society,2011,133(32),12624.135 Scherer F, Anton M, Schillinger U, et al. Gene Therapy,2002,9(2),102.136 Lim J, Clements M A, Dobson J. Plos One,2012,7(12),51350.137 McBain S C, Griesenbach U, Xenariou S, et al. Nanotechnology,2008,19(40),405102.138 Pickard M, Chari D. Nanomedicine,2010,5(2),217.139 Delyagina E, Li W Z, Ma N, et al. Nanomedicine,2011,6(9),1593.140 Yu Y T, Yao Y, Yan H, et al. Molecular Therapy-Nucleic Acids,2016,5,318.141 Lo Y, Chou H, Liao Z, et al. Nanoscale,2015,7,8554.142 Sun S Y, Wang Y L, Zhou R, et al. Theranostics,2017,7(3),677.143 Li Z, Barnes J C, Bosoy A, et al. Chemical Society Review,2012,41,2590.144 Vivero-Escoto J L, Slowing I I, Wu C, et al. Journal of the American Chemical Society,2009,131(10),3462.145 Zhao Z L, Meng H M, Wang N N, et al. Angewandte Chemie-International Edition,2013,52(29),7487.146 Zhang Z, Balogh D, Wang F, et al. Journal of the American Chemical Society,2013,135(5),1934.147 Zhang P H, Cheng F F, Zhou R, et al. Angewandte Chemie-Internatio-nal Edition,2014,53(9),2371.148 He K C, Wang M, Zhao B, et al. Materials Review A:Review Papers,2014,28(7),23(in Chinese).贺旷驰,王蒙,赵斌,等.材料导报:综述篇,2014,28(7),23.149 Chen C, Geng J, Pu F, et al. Angewandte Chemie-International Edition,2011,50(40),882.150 Tivnan A, Orr W S, Gubala V, et al. Plos One,2012,7(5),38129.151 Yu C, Qian L, Uttamchandani M, et al. Angewandte Chemie-International Edition,2015,54(36),10574.152 Pillai R S, Bhattacharyya S N, Filipowicz W. Trends in Cell Biology,2007,17(3),118.153 Filipowicz W.Cell,2005,122(1),17.154 Fernandez-Hernando C, Suarez Y, Rayner K J, et al. Current Opinion in Lipidology,2011,22(2),86.155 Jopling C L, Yi M, Lancaster A M, et al. Science,2005,309(5740),1577.156 Young D D, Connelly C M, Grohmann C, et al. Journal of the American Chemical Society,2010,132(23),7976.157 Connelly C M, Thomas M, Deiters A. Journal of Biomolecular Scree-ning,2012,17(6),822.158 Xia T, Kovochich M, Liong M, et al. American Chemical Society Nano,2009,3(10),3273.159 Hartono S B, Gu W Y, Kleitz F, et al. American Chemical Society Nano,2012,6(3),2104.160 Townson J L, Lin Y S, Agola J O, et al. Journal of the American Chemical Society,2013,135(43),16030.161 Coll C, Bernardos A, Martinez-Manez R, et al. Accounts of Chemical Research,2013,46(2),339.162 Yu C M, Qian L H, Ge J Y, et al. Angewandte Chemie-International Edition,2016,55(32),9272.163 Gasparini G, Bang E K, Molinard G, et al. Journal of the American Chemical Society,2014,136(16),6069.164 Lu J X, Shen H H, Wu Z X, et al. Journal of Materials Chemistry B,2015,3(39),7653.