[1] CHI Z C. Practical Clinical Hepatology(实用临床肝病学)[M]. 2nd Ed. Beijing: People′s Military Medical Press, 2015:173-176.
[2] LEE Y A, WALLACE M C, FRIEDMAN S L. Pathobiology of liver fibrosis: a translational success story [J]. Gut, 2015, 64(5): 830-841.
[3] SCHLAGETER M, TERRACCIANO L M, D′ANGELO S, et al. Histopathology of hepatocellular carcinoma [J]. World J Gastroenterol, 2014, 20(43): 15955-15964.
[4] CHEN Z, JAIN A, LIU H, et al. Targeted drug delivery to hepatic stellate cells for the treatment of liver fibrosis [J]. J Pharmacol Exp Ther, 2019, 370(3): 695-702.
[5] SCHUPPAN D, ASHFAQ-KHAN M, YANG A T, et al. Liver fibrosis: direct antifibrotic agents and targeted therapies [J]. Matrix Biol, 2018, 68-69: 435-451.
[6] BORKHAM-KAMPHORST E, WEISKIRCHEN R. The PDGF system and its antagonists in liver fibrosis [J]. Cytokine & Growth Factor Rev, 2016, 28: 53-61.
[7] PINZANI M, MILANI S, HERBST H, et al. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis [J]. Am J Pathol, 1996, 148(3):785-800.
[8] BELJAARS L, WEERT B, GEERTS A, et al. The preferential homing of a platelet derived growth factor receptor-recognizing macromolecule to fibroblast-like cells in fibrotic tissue [J]. Biochem Pharmacol, 2003, 66(7):1307-1317.
[9] KREYSING J, STMAN A, POLL M V D, et al. Identification of three amino acid residues in the B-chain of platelet-derived growth factor with different importance for binding to PDGF α-and β-receptors [J]. Febs Lett, 1996, 385(3): 181-184.
[10] CLEMENTS J M, BAWDEN L J, BLOXIDGE R E, et al. Two PDGF-B chain residues, arginine 27 and isoleucine 30, mediate receptor binding and activation [J]. EMBO J, 1991, 10(13): 4113-4120.
[11] BREITKOPF K, ROEYEN C, SAWITZA I, et al. Expression patterns of PDGF-A,-B,-C and-D and the PDGF-receptors α and β in activated rat hepatic stellate cells (HSC) [J]. Cytokine, 2005, 31(5):349-357.
[12] IKEDA K, WAKAHARA T, WANG Y Q, et al. In vitro migratory potential of rat quiescent hepatic stellate cells and its augmentation by cell activation [J]. Hepatology, 1999, 29(6):1760-1767.
[13] HAGENS W I, MATTOS A, GREUPINK R, et al. Targeting 15d-prostaglandin J2 to hepatic stellate cells: two options evaluated [J]. Pharm Res, 2007, 24(3): 566-574.
[14] SCHOEMAKER M H, ROTS M G, BELJAARS L, et al. PDGF-receptor beta-targeted adenovirus redirects gene transfer from hepatocytes to activated stellate cells [J]. Mol Pharm, 2008, 5(3): 399-406.
[15] RUCHI B, JAI P, MARIEKE D R, et al. Peptide-modified albumin carrier explored as a novel strategy for a cell-specific delivery of interferon gamma to treat liver fibrosis [J]. Mol Pharm, 2011, 8(5): 1899-1909.
[16] LI F, LI Q H, WANG J Y, et al. Effects of interferon-gamma liposomes targeted to platelet-derived growth factor receptor-beta on hepatic fibrosis in rats [J]. J Controlled Release, 2012, 159(2): 261-270.
[17] TAIMR P, HIGUCHI H, KOCOVA E, et al. Activated stellate cells express the TRAIL receptor-2/death receptor-5 and undergo TRAIL-mediated apoptosis [J]. Hepatology, 2003,33(1):87-95.
[18] LINDBORG M, CORTEZ E, HÖIDÉN-GUTHENBERG I, et al. Engineered high-affinity affibody molecules targeting platelet-derived growth factor receptor β in vivo [J]. J Mol Biol, 2011, 407(2): 298-315.
[19] LI R, LI Z, FENG Y, et al. PDGFRbeta-targeted TRAIL specifically induces apoptosis of activated hepatic stellate cells and ameliorates liver fibrosis [J]. Apoptosis, 2020, 25(1-2): 105-119.
[20] BUHL E M, DJUDJAJ S, KLINKHAMMER B M, et al. Dysregulated mesenchymal PDGFR-β drives kidney fibrosis[J]. EMBO Mol Med, 2020, 2(3):e11021.
[21] SABINE R W, JOHN M, SIMON G. Integrins as therapeutic targets: successes and cancers [J]. Cancers, 2017, 9(9): 110.
[22] LI D, HE L, GUO H, et al. Targeting activated hepatic stellate cells (aHSCs) for liver fibrosis imaging [J]. EJNMMI Res, 2015, 5(1): 71.
[23] SEGUIN L, DESGROSELLIER J S, WEIS S M, et al. Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance [J]. Trends Cell Biol, 2015, 25(4): 234-240.
[24] HUMPHRIES M J. Integrin structure [J]. Biochem Soc Trans, 2000, 28(4): 311-339.
[25] ZHENG Y, LEFTHERIS K. Insights into protein-ligand interactions in integrin complexes: advances in structure determinations [J]. J Med Chem, 2020, 63(11): 5675-5696.
[26] ZHOU X, MURPHY F R, GEHDU N, et al. Engagement of alphavbeta3 integrin regulates proliferation and apoptosis of hepatic stellate cells [J]. J Biol Chem, 2004, 279(23): 23996-4006.
[27] HUANG X W, WANG J Y, LI F, et al. Biochemical characterization of the binding of cyclic RGDyK to hepatic stellate cells [J]. Biochem Pharmacol, 2010, 80(1): 136-143.
[28] JIQING X, YULI C, LEILEI Z, et al. Ultrasound molecular imaging with cRGD-PLGA-PFOB nanoparticles for liver fibrosis staging in a rat model [J]. Oncotarget, 2017, 8(65): 108676-108691.
[29] HENDERSON N C, ARNOLD T D, KATAMURA Y, et al. Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs [J]. Nat Med, 2013, 19(12): 1617-1624.
[30] LI Y, PU S, LIU Q, et al. An integrin-based nanoparticle that targets activated hepatic stellate cells and alleviates liver fibrosis [J]. J Controlled Release, 2019, 303: 77-90.
[31] WANG Q B, HAN Y, JIANG T T, et al. MR Imaging of activated hepatic stellate cells in liver injured by CCl₄ of rats with integrin-targeted ultrasmall superparamagnetic iron oxide [J]. Eur Radiol, 2011, 21(5): 1016-1025.
[32] ZEVON M, GANAPATHY V, KANTAMNENI H, et al. CXCR-4 targeted, short wave infrared (SWIR) emitting nanoprobes for enhanced deep tissue imaging and micrometastatic cancer lesion detection [J]. Small, 2015, 11(47): 6347-6357.
[33] WALD O, PAPPO O, SAFADI R, et al. Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus [J]. Eur J Immunol, 2004, 34(4): 1164-1174.
[34] SUNG Y C, LIU Y C, CHAO P H, et al. Combined delivery of sorafenib and a MEK inhibitor using CXCR4-targeted nanoparticles reduces hepatic fibrosis and prevents tumor development [J]. Theranostics, 2018, 8(4): 894-905.
[35] CHEN Y, HUANG Y, REIBERGER T, et al. Differential effects of sorafenib on liver versus tumor fibrosis mediated by SDF1α/CXCR4 axis and Gr-1+ myeloid cell infiltration in mice [J]. Other, 2014, 59(4): 1435-1447.
[36] ULLAH A, WANG K, WU P, et al. CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFbeta-induced HSC-T6 cells activation [J]. Int J Nanomed, 2019, 14: 2927-2944.
[37] LIU J Y, CHIANG T, LIU C H, et al. Delivery of siRNA using CXCR4-targeted nanoparticles modulates tumor microenvironment and achieves a potent antitumor response in liver cancer [J]. Mol Ther, 2015, 23(11): 1772-1782.
[38] KULARATNE S A, DESHMUKH V, MA J, et al. A CXCR4-targeted site-specific antibody-drug conjugate [J]. Angew Chem Int Ed Engl, 2014, 53(44): 11863-11867.
[39] FALGAS A, PALLARES V, UNZUETA U, et al. A CXCR4-targeted nanocarrier achieves highly selective tumor uptake in diffuse large B-cell lymphoma mouse models [J]. Haematologica, 2020, 105(3): 741-753.
[40] UNZUETA U, CESPEDES M V, FERRER-MIRALLES N, et al. Intracellular CXCR4(+) cell targeting with T22-empowered protein-only nanoparticles [J]. Int J Nanomed, 2012, 7: 4533-4544.
[41] MCCALLION C, PETERS A D, BOOTH A, et al. Dual-action CXCR4-targeting liposomes in leukemia: function blocking and drug delivery [J]. Blood Adv, 2019, 3(14): 2069-2081.
[42] LORÉAL O, CLÉMENT B, SCHUPPAN D, et al. Distribution and cellular origin of collagen VI during development and in cirrhosis [J]. Gastroenterology, 1992, 102(3): 980-987.
[43] POPOV Y, SCHUPPAN D. Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies [J]. Hepatology, 2009, 50(4): 1294-1306.
[44] MARCELINO J, MCDEVITT C A. Attachment of articular cartilage chondrocytes to the tissue form of type VI collagen [J]. Biochim Biophys Acta, 1995, 1249(2): 180-188.
[45] BELJAARS L, MOLEMA G, SCHUPPAN D, et al. Successful targeting to rat hepatic stellate cells using albumin modified with cyclic peptides that recognize the collagen type VI receptor [J]. J Biol Chem, 2000, 275(17): 12743-12751.
[46] DU S L, PAN H, LU W Y, et al. Cyclic Arg-Gly-Asp peptide-labeled liposomes for targeting drug therapy of hepatic fibrosis in rats [J]. J Pharmacol Exp Ther, 2007, 322(2): 560-568.
[47] LI F, SUN J Y, WANG J Y, et al. Effect of hepatocyte growth factor encapsulated in targeted liposomes on liver cirrhosis [J]. J Controlled Release, 2008, 131(1): 77-82.
[48] YANG J, HOU Y, JI G, et al. Targeted delivery of the RGD-labeled biodegradable polymersomes loaded with the hydrophilic drug oxymatrine on cultured hepatic stellate cells and liver fibrosis in rats [J]. Eur J Pharm Sci, 2014, 52: 180-190.
[49] TRIM N, MORGAN S, EVANS M, et al. Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation [J]. Am J Pathol, 2000, 156(4): 1235-1243.
[50] ASAHINA K, TSAI S Y, LI P, et al. Mesenchymal origin of hepatic stellate cells, submesothelial cells, and perivascular mesenchymal cells during mouse liver development [J]. Hepatology, 2009, 49(3): 998-1011.
[51] CASSIMAN D, DENEF C, DESMET V J, et al. Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors [J]. Hepatology, 2001, 33(1): 148-158.
[52] HE X L, GARCIA K C. Structure of nerve growth factor complexed with the shared neurotrophin receptor p75 [J]. Science, 2004,304(5672):870-875.
[53] SCHACHTRUP C, LE MOAN N, PASSINO M A, et al. Hepatic stellate cells and astrocytes: stars of scar formation and tissue repair [J]. Cell Cycle, 2011, 10(11): 1764-1771.
[54] AMORAS EDA S, GOMES S T, FREITAS F B, et al. NGF and P75NTR gene expression is associated with the hepatic fibrosis stage due to viral and non-viral causes [J]. PLoS One, 2015, 10(3): e0121754.
[55] ASAI K, TAMAKAWA S, YAMAMOTO M, et al. Activated hepatic stellate cells overexpress p75NTR after partial hepatectomy and undergo apoptosis on nerve growth factor stimulation [J]. Liver International, 2006, 26(5): 595-603.
[56] REETZ J, GENZ B, MEIER C, et al. Development of adenoviral delivery systems to target hepatic stellate cells in vivo [J]. PLoS One, 2013, 8(6): e67091.
[57] SCHON H T, BARTNECK M, BORKHAM-KAMPHORST E, et al. Pharmacological intervention in hepatic stellate cell activation and hepatic fibrosis [J]. Front Pharmacol, 2016, 7: 33.
[58] HAISMA H J, GRILL J, CURIEL D T, et al. Targeting of adenoviral vectors through a bispecific single-chain antibody[J]. Cancer Gene Ther, 2000, 7(6):901-904.
[59] O'RIORDAN C R, LACHAPELLE A, DELGADO C, et al. PEGylation of adenovirus with retention of infectivity and protection from neutralizing antibody in vitro and in vivo [J]. Human Gene Ther, 1999, 10(8): 1349-1358.
[60] ISE H, KOBAYASHI S, GOTO M, et al. Vimentin and desmin possess GlcNAc-binding lectin-like properties on cell surfaces [J]. Glycobiology, 2010, 20(7): 843-864.
[61] GOLDIE K N, WEDIG T, MITRA A K, et al. Dissecting the 3-D structure of vimentin intermediate filaments by cryo-electron tomography [J]. J Struct Biol, 2007, 158(3): 378-385.
[62] PAULIN D, LI Z. Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle [J]. Exp Cell Res, 2004, 301(1): 1-7.
[63] ISE H, GOTO M, KOMURA K, et al. Engulfment and clearance of apoptotic cells based on a GlcNAc-binding lectin-like property of surface vimentin [J]. Glycobiology, 2012, 22(6): 788-805.
[64] IVASKA J, PALLARI H M, NEVO J, et al. Novel functions of vimentin in cell adhesion, migration, and signaling [J]. Exp Cell Res, 2007, 313(10): 2050-2062.
[65] NIKI T, PEKNY M, HELLEMANS K, et al. Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells [J]. Hepatology, 1999, 29(2): 520-527.
[66] KIM S J, ISE H, GOTO M, et al. Interactions of vimentin-or desmin-expressing liver cells with N-acetylglucosamine-bearing polymers [J]. Biomaterials, 2012, 33(7): 2154-2164.
[67] KIM S J, ISE H, KIM E, et al. Imaging and therapy of liver fibrosis using bioreducible polyethylenimine/siRNA complexes conjugated with N-acetylglucosamine as a targeting moiety [J]. Biomaterials, 2013, 34(27): 6504-6514.
[68] ZHANG D, ZHUANG R, GUO Z, et al. Desmin-and vimentin-mediated hepatic stellate cell-targeting radiotracer (99m)Tc-GlcNAc-PEI for liver fibrosis imaging with SPECT [J]. Theranostics, 2018, 8(5): 1340-1349.
[69] ASO S, ISE H, TAKAHASHI M, et al. Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro [J]. J Controlled Release, 2007, 122(2): 189-198.
[70] MORGAN D O, EDMAN J C, STANGRING D N, et al. Insulin-like growth factor II receptor as a multifunctional binding protein [J]. Nature, 1987, 329(6137): 2636-2658.
[71] ZHAO Z, LI Y, JAIN A, et al. Development of a peptide-modified siRNA nanocomplex for hepatic stellate cells [J]. Nanomedicine, 2018, 14(1): 51-61.
[72] BLESER P J D, JANNES P, BUUL-OFFERS S C V, et al. Insulinlike growth factor-II/mannose 6-phosphate receptor is expressed on cc1 4-exposed rat fat-storing cells and facilitates activation of latent transforming growth factor-β in cocultures with sinusoidal endothelial cells [J]. Hepatology, 1995, 21(5): 1429-1437.
[73] CAVAL T, ZHU J, TIAN W, et al. Targeted analysis of lysosomal directed proteins and their sites of mannose-6-phosphate modification [J]. Mol Cell Proteomics, 2019, 18(1): 16-27.
[74] WEINER J A, CHEN A, DAVIS B H. E-box-binding repressor is down-regulated in hepatic stellate cells during up-regulation of mannose 6-phosphate/insulin-like growth factor-II receptor expression in early hepatic fibrogenesis [J]. J Biol Chem, 1998, 273(26): 15913-15919.
[75] GREUPINK R, BAKKER H I, VAN GOOR H, et al. Mannose-6-phosphate/insulin-like growth factor-II receptors may represent a target for the selective delivery of mycophenolic acid to fibrogenic cells [J]. Pharm Res, 2006, 23(8): 1827-1834.
[76] KOVACINA K S, STEELE-PERKINS G, PURCHIO A F, et al. Interactions of recombinant and platelet transforming growth factor-beta 1 precursor with the insulin-like growth factor II/mannose 6-phosphate receptor [J]. Biochem Biophys Res Comm, 1989, 160(1): 393-403.
[77] PURCHIO A F, COOPER J A, BRUNNER A M, et al. Identification of mannose 6-phosphate in two asparagine-linked sugar chains of recombinant transforming growth factor-beta 1 precursor [J]. J Biol Chem, 1988, 263(28): 14211-14215.
[78] DENNIS P A, RIFKIN D B. Cellular activation of latent transforming growth factor beta requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type Ⅱ receptor [J]. Proc Nat Acad Sci, 1991, 88(2): 580-584.
[79] BELJAARS L, MOLEMA G, WEERT B, et al. Albumin modified with mannose 6-phosphate: a potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells [J]. Hepatology (Baltimore, Md), 1999, 29(5): 1486-1493.
[80] GREUPINK R, BAKKER H I, BOUMA W, et al. The antiproliferative drug doxorubicin inhibits liver fibrosis in bile duct-ligated rats and can be selectively delivered to hepatic stellate cells in vivo [J]. J Pharmacol Exp Ther, 2006, 317(2): 514-521.
[81] GONZALO T, BELJAARS L, VAN DE BOVENKAMP M, et al. Local inhibition of liver fibrosis by specific delivery of a platelet-derived growth factor kinase inhibitor to hepatic stellate cells [J]. J Pharmacol Exp Ther, 2007, 321(3): 856-865.
[82] MORENO M, GONZALO T, KOK R J, et al. Reduction of advanced liver fibrosis by short-term targeted delivery of an angiotensin receptor blocker to hepatic stellate cells in rats [J]. Hepatology, 2010, 51(3): 942-952.
[83] YE Z, CHENG K, GUNTAKA R V, et al. Receptor-mediated hepatic uptake of M6P-BSA-conjugated triplex-forming oligonucleotides in rats [J]. Bioconjug Chem, 2006, 17(3): 823-830.