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Asialoglycoprotein Receptor and Targeting Strategies

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Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 39))

Abstract

The asialoglycoprotein receptor is a calcium-dependent, carbohydrate-specific, type C lectin, which is majorly present in the plasma membrane of liver cells (hepatocytes). The high liver specificity, efficient internalization rate, and ready accessibility to the vasculature present great potential of this receptor for use in site-specific targeting of nano-delivery systems for diagnostic and therapeutic applications in liver diseases with negligible nontarget toxicity. This chapter provides a detailed discussion on the receptor expression, structure, binding, ligands, and asialoglycoprotein receptor-mediated hepatocyte-targeted delivery systems. It also discusses the clinical relevance of the receptor in numerous liver afflictions along with its application in liver diagnostics.

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Abbreviations

5-FU:

5-Fluorouracil

AA:

Antibiotin antibody

AF:

Asialofetuin

AG:

Arabinogalactan

AI-CAH:

Autoimmune-type chronic active hepatitis

AIH:

Autoimmune hepatitis

ApoE:

Apolipoprotein E

ASGP-R:

Asialoglycoprotein receptor

asODN:

Antisense oligonucleotides

ASOR:

Asialoorosomucoid AuNPs@PDA Gold nanoparticles@Polydopamine

BDICA:

Triiodobenzene compound

BNLCL2:

Mouse embryonic liver cells

BSA:

Bovine serum albumin

C4-Chol:

Cholesten-5-yloxy-N-(4-((1-imino-2-d-thiogalactosylethyl)amino) butyl)formamide

CDE:

Cyclodextrin conjugated PAMAM dendrimer

CMC:

Carboxymethyl chitosan

CMD:

Carboxymethyl-dextran

CPDC:

Cationic polycarbonate diblock copolymer

CRD:

Carbohydrate recognition domain

CTG:

Cholesterylated thiogalactoside

DDMAP:

Dimyristoyl diacyltrimethylammonium propane

DOX:

Doxorubicin

DPEA:

Dioleoylphosphatidyl ethanolamine

DTPA:

Diethylenetriamine pentaacetic acid

EGFR-ERK:

Epidermal growth factor receptor-extracellular signal regulated kinases

Gal:

Galactose

GalNAc:

N-acetylgalactosamine

GDPA:

Gadolinium diethylenetriamine pentaacetic acid

GO:

Graphene oxide

H-bond:

Hydrogen bond

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HepG2:

Hepatocellular carcinoma cell line

HSA:

Human serum albumin

IgA:

Immunoglobulins A

IL:

Interleukin

KC:

Kupffer cell

LA:

Lactobionic acid

Lac:

Lactosaminated

LDL:

Low-density lipoproteins

LSP:

Liver-specific protein

MHV:

Mouse hepatitis virus

MRI:

Magnetic resonance imaging

N-HPMA:

N-(2hydroxypropyl) methacrylamide

N-LDLPTA:

N-lactosyl-dioleoylphosphatidylethanolamine

NPs:

Nanoparticles

p(VLA-co-VNI-co-V2DTPA):

Poly(vinylbenzyl-O-b-D-galactopyranosyl-D-gluconamide)-co-N-p-vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono)nicotinate-co-5,8-bis(carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid

PAA:

Poly(amidoamine)

PAE/PLGA:

Poly(β-amino ester)/poly(lactic-co-glycolic acid)

PEC:

Poly(ε-caprolactone)

PEG:

Polyethylene glycol

PEG-PEC:

Poly(ethylene glycol)-poly(ε-caprolactone)

PEI:

Polyethylenimine

PGA:

Poly-γ-glutamic acid

PGEA:

Poly(glycidyl-ethanolamine)

PLA:

Polylactic acid

PLGA:

Poly(lactic-co-glycolic acid)

PLL:

Poly-L-lysine

PNIPAm:

Poly (N-isopropylacrylamide)

PTX:

Paclitaxel

RBV:

Ribavarin

siRNA:

Small interfering RNA

SPECT:

Single-photon emission computed tomography

TAB:

Tetraacetylbromo

TNF:

Tumor necrosis factor

TPGS:

Tocopherol polyethylene glycol succinate

References

  1. D’Souza AA, Devarajan PV. Asialoglycoprotein receptor mediated hepatocyte targeting - Strategies and applications. J Control Release. 2015;203:126–39.

    Article  PubMed  CAS  Google Scholar 

  2. Kedderis GL, Held SD. Prediction of furan pharmacokinetics from hepatocyte studies: comparison of bioactivation and hepatic dosimetry in rats, mice, and humans. Toxicol Appl Pharmacol. 1996;140(1):124–30.

    Article  CAS  PubMed  Google Scholar 

  3. Ashwell G, Harford J. Carbohydrate-specific receptors of the liver. Annu Rev Biochem. 1982;51(1):531–54.

    Article  CAS  PubMed  Google Scholar 

  4. Grewal PK. The Ashwell–Morell receptor. In: Methods in enzymology, vol. 479: Academic Press; 2010. p. 223–41. United States of America.

    Google Scholar 

  5. Spiess M. The asialoglycoprotein receptor: a model for endocytic transport receptors. Biochemistry. 1990;29(43):10009–18.

    Article  CAS  PubMed  Google Scholar 

  6. Roggenbuck D, Mytilinaiou MG, Lapin SV, Reinhold D, Conrad K. Asialoglycoprotein receptor (ASGPR): a peculiar target of liver-specific autoimmunity. Auto Immun Highlights. 2012;3(3):119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Weigel PH. Characterization of the asialoglycoprotein receptor on isolated rat hepatocytes. J Biol Chem. 1980;255(13):6111–20.

    CAS  PubMed  Google Scholar 

  8. Li Y, Huang G, Diakur J, Wiebe LI. Targeted delivery of macromolecular drugs: asialoglycoprotein receptor (ASGPR) expression by selected hepatoma cell lines used in antiviral drug development. Curr Drug Deliv. 2008;5(4):299–302.

    Article  CAS  PubMed  Google Scholar 

  9. Schwartz AL, Ashwell G. The hepatic asialoglycoprotein receptor. Crit Rev Biochem. 1984;16(3):207–33.

    Article  CAS  Google Scholar 

  10. Park JH, Cho EW, Shin SY, Lee YJ, Kim KL. Detection of the asialoglycoprotein receptor on cell lines of extrahepatic origin. Biochem Biophys Res Commun. 1998;244(1):304–11.

    Article  CAS  PubMed  Google Scholar 

  11. Rigopoulou EI, Roggenbuck D, Smyk DS, Liaskos C, Mytilinaiou MG, Feist E, Conrad K, Bogdanos DP. Asialoglycoprotein receptor (ASGPR) as target autoantigen in liver autoimmunity: lost and found. Autoimmun Rev. 2012;12(2):260–9.

    Article  CAS  PubMed  Google Scholar 

  12. Dotzauer A, Gebhardt U, Bieback K, Göttke U, Kracke A, Mages J, Lemon SM, Vallbracht A. Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor. J Virol. 2000;74(23):10950–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yang J, Wang F, Tian L, Su J, Zhu X, Lin L, Ding X, Wang X, Wang S. Fibronectin and asialoglyprotein receptor mediate hepatitis B surface antigen binding to the cell surface. Arch Virol. 2010;155(6):881–8.

    Article  CAS  PubMed  Google Scholar 

  14. Treichel U, zum Büschenfelde KH, Stockert RJ, Poralla T, Gerken G. The asialoglycoprotein receptor mediates hepatic binding and uptake of natural hepatitis B virus particles derived from viraemic carriers. J Gen Virol. 1994;75(11):3021–9.

    Article  CAS  PubMed  Google Scholar 

  15. Stockert RJ. The asialoglycoprotein receptor: relationships between structure, function, and expression. Physiol Rev. 1995;75(3):591–609.

    Article  CAS  PubMed  Google Scholar 

  16. Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn LD. Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol. 2003;77(1):546–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Becker S, Spiess M, Klenk HD. The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol. 1995;76(2):393–9.

    Article  CAS  PubMed  Google Scholar 

  18. Grewal PK, Uchiyama S, Ditto D, Varki N, Le DT, Nizet V, Marth JD. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med. 2008;14(6):648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ueno S, Mojic M, Ohashi Y, Higashi N, Hayakawa Y, Irimura T. Asialoglycoprotein receptor promotes cancer metastasis by activating the EGFR–ERK pathway. Cancer Res. 2011;71(20):6419–27.

    Article  CAS  PubMed  Google Scholar 

  20. Nakaya R, Kohgo Y, Mogi Y, Nakajima M, Kato J, Niitsu Y. Regulation of asialoglycoprotein receptor synthesis by inflammation-related cytokines in HepG2 cells. J Gastroenterol. 1994;29(1):24–30.

    Article  CAS  PubMed  Google Scholar 

  21. Poralla T, Treichel U, Löhr H, Fleischer B. The asialoglycoprotein receptor as target structure in autoimmune liver diseases. Semin Liver Dis. 1991;11(03):215–22. Thieme Medical Publishers, Inc.

    Article  CAS  PubMed  Google Scholar 

  22. McFarlane IG, McFarlane BM, Major GN, Tolley P, Williams R. Identification of the hepatic asialo-glycoprotein receptor (hepatic lectin) as a component of liver specific membrane lipoprotein (LSP). Clin Exp Immunol. 1984;55(2):347.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Witzigmann D, Quagliata L, Schenk SH, Quintavalle C, Terracciano LM, Huwyler J. Variable asialoglycoprotein receptor 1 expression in liver disease: implications for therapeutic intervention. Hepatol Res. 2016;46(7):686–96.

    Article  CAS  PubMed  Google Scholar 

  24. Villalta D, Mytilinaiou MG, Elsner M, Hentschel C, Cuccato J, Somma V, Schierack P, Roggenbuck D, Bogdanos DP. Autoantibodies to asialoglycoprotein receptor (ASGPR) in patients with autoimmune liver diseases. Clin Chim Acta. 2015;450:1–5.

    Article  CAS  PubMed  Google Scholar 

  25. Sawamura T, Nakada H, Hazama H, Shiozaki Y, Sameshima Y, Tashiro Y. Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma: asialoglycoprotein receptor in cirrhosis and liver cell carcinoma. Gastroenterology. 1984;87(6):1217–21.

    Article  CAS  PubMed  Google Scholar 

  26. Virgolini I, Müller C, Klepetko W, Angelberger P, Bergmann H, O’Grady J, Sinzinger H. Decreased hepatic function in patients with hepatoma or liver metastasis monitored by a hepatocyte specific galactosylated radioligand. Br J Cancer. 1990;61(6):937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. DODEUR M, DURAND D, DUMONT J, DURAND G, FEGER J, AGNERAY J. Effects of streptozotocin-induced diabetes mellitus on the binding and uptake of asialoorosomucoïd by isolated hepatocytes from rats. Eur J Biochem. 1982;123(2):383–7.

    Article  CAS  PubMed  Google Scholar 

  28. Burgess JB, Baenziger JU, Brown WR. Abnormal surface distribution of the human asialoglycoprotein receptor in cirrhosis. Hepatology. 1992;15(4):702–6.

    Article  CAS  PubMed  Google Scholar 

  29. Marshall JS, Green AM, Pensky J, Williams S, Zinn A, Carlson DM. Measurement of circulating desialylated glycoproteins and correlation with hepatocellular damage. J Clin Invest. 1974;54(3):555–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Trere D, Fiume L, De Giorgi LB, Di Stefano G, Migaldi M, Derenzini M. The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells. Br J Cancer. 1999;81(3):404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bischoff J, Lodish HF. Two asialoglycoprotein receptor polypeptides in human hepatoma cells. J Biol Chem. 1987;262(24):11825–32.

    CAS  PubMed  Google Scholar 

  32. Meier M, Bider MD, Malashkevich VN, Spiess M, Burkhard P. Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor. J Mol Biol. 2000;300(4):857–65.

    Article  CAS  PubMed  Google Scholar 

  33. Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. Proc Natl Acad Sci. 1985;82(19):6465–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Harris RL, Van den Berg CW, Bowen DJ. ASGR1 and ASGR2, the genes that encode the asialoglycoprotein receptor (Ashwell receptor), are expressed in peripheral blood monocytes and show interindividual differences in transcript profile. Mol Biol Int. 2012;2012:1.

    Article  CAS  Google Scholar 

  35. Henis YI, Katzir Z, Shia MA, Lodish HF. Oligomeric structure of the human asialoglycoprotein receptor: nature and stoichiometry of mutual complexes containing H1 and H2 polypeptides assessed by fluorescence photobleaching recovery. J Cell Biol. 1990;111(4):1409–18.

    Article  CAS  PubMed  Google Scholar 

  36. Braiterman LT, Chance SC, Porter WR, Lee YC, Townsend RR, Hubbard AL. The major subunit of the rat asialoglycoprotein receptor can function alone as a receptor. J Biol Chem. 1989;264(3):1682–8.

    CAS  PubMed  Google Scholar 

  37. Ishibashi S, Hammer RE, Herz J. Asialoglycoprotein receptor deficiency in mice lacking the minor receptor subunit. J Biol Chem. 1994;269(45):27803–6.

    CAS  PubMed  Google Scholar 

  38. Shia MA, Lodish HF. The two subunits of the human asialoglycoprotein receptor have different fates when expressed alone in fibroblasts. Proc Natl Acad Sci. 1989;86(4):1158–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tozawa RI, Ishibashi S, Osuga JI, Yamamoto K, Yagyu H, Ohashi K, Tamura Y, Yahagi N, Iizuka Y, Okazaki H, Harada K. Asialoglycoprotein receptor deficiency in mice lacking the major receptor subunit its obligate requirement for the stable expression of oligomeric receptor. J Biol Chem. 2001;276(16):12624–8.

    Article  CAS  PubMed  Google Scholar 

  40. Valladeau J, Duvert-Frances V, Pin JJ, Kleijmeer MJ, Ait-Yahia S, Ravel O, Vincent C, Vega F, Helms A, Gorman D, Zurawski SM. Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol. 2001;167(10):5767–74.

    Article  CAS  PubMed  Google Scholar 

  41. Massarelli I, Murgia L, Bianucci A, Chiellini F, Chiellini E. Understanding the selectivity mechanism of the human asialoglycoprotein receptor (ASGP-R) toward gal-and man-type ligands for predicting interactions with exogenous sugars. Int J Mol Sci. 2007;8(1):13–28.

    Article  CAS  PubMed Central  Google Scholar 

  42. Mcabee DD, Jiang X, WALSH KB. Lactoferrin binding to the rat asialoglycoprotein receptor requires the receptor’s lectin properties. Biochem J. 2000;348(1):113–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Onizuka T, Shimizu H, Moriwaki Y, Nakano T, Kanai S, Shimada I, Takahashi H. NMR study of ligand release from asialoglycoprotein receptor under solution conditions in early endosomes. FEBS J. 2012;279(15):2645–56.

    Article  CAS  PubMed  Google Scholar 

  44. Weigel PH, Yik JH. Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochim Biophys Acta. 2002;1572(2–3):341–63.

    Article  CAS  PubMed  Google Scholar 

  45. Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA. An internal signal sequence for membrane insertion. J Biol Chem. 1985;260(4):1979–82.

    CAS  PubMed  Google Scholar 

  46. Ramadugu SK, Chung YH, Fuentes EJ, Rice KG, Margulis CJ. In silico prediction of the 3D structure of trimeric asialoglycoprotein receptor bound to triantennary oligosaccharide. J Am Chem Soc. 2010;132(26):9087–95.

    Article  CAS  PubMed  Google Scholar 

  47. Bider MD, Wahlberg JM, Kammerer RA, Spiess M. The oligomerization domain of the asialoglycoprotein receptor preferentially forms 2: 2 heterotetramers in vitro. J Biol Chem. 1996;271(50):31996–2001.

    Article  CAS  PubMed  Google Scholar 

  48. D’Souza AA, Jain P, Galdhar CN, Samad A, Degani MS, Devarajan PV. Comparative in silico–in vivo evaluation of ASGP-R ligands for hepatic targeting of curcumin Gantrez nanoparticles. AAPS J. 2013;15(3):696–706.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Braun JR, Willnow TE, Ishibashi S, Ashwell G, Herz J. The major subunit of the asialoglycoprotein receptor is expressed on the hepatocellular surface in mice lacking the minor receptor subunit. J Biol Chem. 1996;271(35):21160–6.

    Article  CAS  PubMed  Google Scholar 

  50. Kolatkar AR, Weis WI. Structural basis of galactose recognition by C-type animal lectins. J Biol Chem. 1996;271(12):6679–85.

    Article  CAS  PubMed  Google Scholar 

  51. Huang X, Leroux JC, Castagner B. Well-defined multivalent ligands for hepatocytes targeting via asialoglycoprotein receptor. Bioconjug Chem. 2016;28(2):283–95.

    Article  PubMed  CAS  Google Scholar 

  52. Marth JD, Grewal PK. Mammalian glycosylation in immunity. Nat Rev Immunol. 2008;8(11):874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Weis WI, Taylor ME, Drickamer K. The C-type lectin superfamily in the immune system. Immunol Rev. 1998;163(1):19–34.

    Article  CAS  PubMed  Google Scholar 

  54. Rohilla R, Garg T, Goyal AK, Rath G. Herbal and polymeric approaches for liver-targeting drug delivery: novel strategies and their significance. Drug Deliv. 2016;23(5):1645–61.

    CAS  PubMed  Google Scholar 

  55. Maitani Y, Kawano K, Yamada K, Nagai T, Takayama K. Efficiency of liposomes surface-modified with soybean-derived sterylglucoside as a liver targeting carrier in HepG2 cells. J Control Release. 2001;75(3):381–9.

    Article  CAS  PubMed  Google Scholar 

  56. Selim KK, Ha YS, Kim SJ, Chang Y, Kim TJ, Lee GH, Kang IK. Surface modification of magnetite nanoparticles using lactobionic acid and their interaction with hepatocytes. Biomaterials. 2007;28(4):710–6.

    Article  CAS  Google Scholar 

  57. Li M, Zhang W, Wang B, Gao Y, Song Z, Zheng QC. Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma. Int J Nanomedicine. 2016;11:5645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hu HM, Zhang X, Zhong NQ, Pan SR. Study on galactose–poly (ethylene glycol)–poly (L-lysine) as novel gene vector for targeting hepatocytes in vitro. J Biomater Sci Polym Ed. 2012;23(5):677–95.

    Article  CAS  PubMed  Google Scholar 

  59. Wu GY, Wu CH. Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. J Biol Chem. 1987;262(10):4429–32.

    CAS  PubMed  Google Scholar 

  60. Robinson MA, Charlton ST, Garnier P, Wang XT, Davis SS, Perkins AC, Frier M, Duncan R, Savage TJ, Wyatt DA, Watson SA. LEAPT: lectin-directed enzyme-activated prodrug therapy. Proc Natl Acad Sci. 2004;101(40):14527–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Huang Y. Preclinical and clinical advances of GalNAc-decorated nucleic acid therapeutics. Mol Ther Nucleic Acids. 2017;6:116–32.

    Article  CAS  PubMed  Google Scholar 

  62. Ivanenkov YA, Maklakova SY, Beloglazkina EK, Zyk NV, Nazarenko AG, Tonevitsky AG, Kotelianski VE, Majouga AG. Development of liver cell-targeted drug delivery systems: experimental approaches. Russ Chem Rev. 2017;86(8):750.

    Article  CAS  Google Scholar 

  63. Fiume L, Di Stefano G, inventors; UNIVERSITA’DI BOLOGNA DIPARTIMENTO DI PATOLOGIA SPERIMENTALE, assignee. Use of conjugates of doxorubicin with lactosaminated albumin. United States patent application US 12/067,211. 2008 Sep 18.

    Google Scholar 

  64. Singh Y, Palombo M, Sinko PJ. Recent trends in targeted anticancer prodrug and conjugate design. Curr Med Chem. 2008;15(18):1802–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Fiume L, Mattioli A, Balboni PG, Tognon M, Barbanti-Brodano G, De Vries J, Wieland T. Enhanced inhibition of virus DNA synthesis in hepatocytes by trifluorothymidine coupled to asialofetuin. FEBS Lett. 1979;103(1):47–51.

    Article  CAS  PubMed  Google Scholar 

  66. Fiume L, Mattioli A, Busi C, Accorsi C. Selective penetration and pharmacological activity of lactosaminated albumin conjugates of adenine arabinoside 5-monophosphate (ara-AMP) in mouse liver. Gut. 1984;25(12):1392–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Muro S. Challenges in design and characterization of ligand-targeted drug delivery systems. J Control Release. 2012;164(2):125–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wu J, Yuan J, Ye B, Wu Y, Xu Z, Chen J, Chen J. Dual-responsive core crosslinking glycopolymer-drug conjugates nanoparticles for precise hepatocarcinoma therapy. Front Pharmacol. 2018;9

    Google Scholar 

  69. Ishihara T, Kano A, Obara K, Saito M, Chen X, Park TG, Akaike T, Maruyama A. Nuclear localization and antisense effect of PNA internalized by ASGP-R-mediated endocytosis with protein/DNA conjugates. J Control Release. 2011;155(1):34–9.

    Article  CAS  PubMed  Google Scholar 

  70. Ma Y, Chen H, Su S, Wang T, Zhang C, Fida G, Cui S, Zhao J, Gu Y. Galactose as Broad ligand for multiple tumor imaging and therapy. J Cancer. 2015;6(7):658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Willoughby JL, Chan A, Sehgal A, Butler JS, Nair JK, Racie T, Shulga-Morskaya S, Nguyen T, Qian K, Yucius K, Charisse K. Evaluation of GalNAc-siRNA conjugate activity in pre-clinical animal models with reduced asialoglycoprotein receptor expression. Mol Ther. 2018;26(1):105–14.

    Article  CAS  PubMed  Google Scholar 

  72. Varshosaz J, Asheghali F. Chondroitin/doxorubicin nanoparticulate polyelectrolyte complex for targeted delivery to HepG2 cells. IET Nanobiotechnol. 2016;11(2):164–72.

    Article  PubMed Central  Google Scholar 

  73. Yu CY, Wang YM, Li NM, Liu GS, Yang S, Tang GT, He DX, Tan XW, Wei H. In vitro and in vivo evaluation of pectin-based nanoparticles for hepatocellular carcinoma drug chemotherapy. Mol Pharm. 2014;11(2):638–44.

    Article  CAS  PubMed  Google Scholar 

  74. Nair JK, Willoughby JL, Chan A, Charisse K, Alam MR, Wang Q, et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc. 2014;136(49):16958–61.

    Article  CAS  PubMed  Google Scholar 

  75. Ong ZY, Yang C, Gao SJ, Ke XY, Hedrick JL, Yan YY. Galactose-functionalized cationic polycarbonate diblock copolymer for targeted gene delivery to hepatocytes. Macromol Rapid Commun. 2013;34(21):1714–20.

    Article  CAS  PubMed  Google Scholar 

  76. Yang XC, Niu YL, Zhao NN, Mao C, Xu FJ. A biocleavable pullulan-based vector via ATRP for liver cell-targeting gene delivery. Biomaterials. 2014;35(12):3873–84.

    Article  CAS  PubMed  Google Scholar 

  77. Dehshahri A, Kazemi Oskuee R, Thomas Shier W, Ramezani M. β-Galactosylated alkyl-oligoamine derivatives of polyethylenimine enhanced pDNA delivery into hepatic cells with reduced toxicity. Curr Nanosci. 2012;8(4):548–55.

    Article  CAS  Google Scholar 

  78. Di Stefano G, Colonna FP, Bongini A, Busi C, Mattioli A, Fiume L. Ribavirin conjugated with lactosaminated poly-L-lysine: selective delivery to the liver and increased antiviral activity in mice with viral hepatitis. Biochem Pharmacol. 1997;54(3):357–63.

    Article  PubMed  Google Scholar 

  79. Ma J, Huang C, Yao X, Shi C, Sun L, Yuan L, Lei P, Zhu H, Liu H, Wu X, Ning Q. Inhibition of hepatitis B virus and induction of hepatoma cell apoptosis by ASGPR-directed delivery of shRNAs. PLoS One. 2012;7(10):e46096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tomiya N, Jardim JG, Hou J, Pastrana-Mena R, Dinglasan RR, Lee YC. Liver-targeting of primaquine-(poly-γ-glutamic acid) and its degradation in rat hepatocytes. Bioorg Med Chem. 2013;21(17):5275–81.

    Article  CAS  PubMed  Google Scholar 

  81. Hashida M, Hirabayashi H, Nishikawa M, Takakura Y. Targeted delivery of drugs and proteins to the liver via receptor-mediated endocytosis. J Control Release. 1997;46(1–2):129–37.

    Article  CAS  Google Scholar 

  82. Nishikawa M, Kamijo A, Fujita T, Takakura Y, Sezaki H, Hashida M. Synthesis and pharmacokinetics of a new liver-specific carrier, glycosylated carboxymethyl-dextran, and its application to drug targeting. Pharm Res. 1993;10(9):1253–61.

    Article  CAS  PubMed  Google Scholar 

  83. McMahon A, O’neill MJ, Gomez E, Donohue R, Forde D, Darcy R, O’driscoll CM. Targeted gene delivery to hepatocytes with galactosylated amphiphilic cyclodextrins. J Pharm Pharmacol. 2012;64(8):1063–73.

    Article  CAS  PubMed  Google Scholar 

  84. Popielarski SR, Pun SH, Davis ME. A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 1. Synthesis and characterization. Bioconjug Chem. 2005;16(5):1063–70.

    Article  CAS  PubMed  Google Scholar 

  85. Biessen EA, Beuting DM, Vietsch H, Bijsterbosch MK, Van Berkel TJ. Specific targeting of the antiviral drug 5-iodo 2′-deoxyuridine to the parenchymal liver cell using lactosylated poly-L-lysine. J Hepatol. 1994;21(5):806–15.

    Article  CAS  PubMed  Google Scholar 

  86. Murao A, Nishikawa M, Managit C, Wong J, Kawakami S, Yamashita F, Hashida M. Targeting efficiency of galactosylated liposomes to hepatocytes in vivo: effect of lipid composition. Pharm Res. 2002;19(12):1808–14.

    Article  CAS  PubMed  Google Scholar 

  87. Naicker K, Ariatti M, Singh M. PEGylated galactosylated cationic liposomes for hepatocytic gene delivery. Colloids Surf B: Biointerfaces. 2014;122:482–90.

    Article  CAS  PubMed  Google Scholar 

  88. Nishikawa M, Ohtsubo Y, Ohno J, Fujita T, Koyama Y, Yamashita F, Hashida M, Sezaki H. Pharmacokinetics of receptor-mediated hepatic uptake of glycosylated albumin in mice. Int J Pharm. 1992;85(1–3):75–85.

    Article  CAS  Google Scholar 

  89. Zhang YN, Poon W, Tavares AJ, McGilvray ID, Chan WC. Nanoparticle–liver interactions: cellular uptake and hepatobiliary elimination. J Control Release. 2016;240:332–48.

    Article  CAS  PubMed  Google Scholar 

  90. Arima H, Motoyama K, Higashi T. Potential use of cyclodextrins as drug carriers and active pharmaceutical ingredients. Chem Pharm Bull. 2017;65(4):341–8.

    Article  CAS  Google Scholar 

  91. Quan G, Pan X, Wang Z, Wu Q, Li G, Dian L, Chen B, Wu C. Lactosaminated mesoporous silica nanoparticles for asialoglycoprotein receptor targeted anticancer drug delivery. J Nanobiotechnol. 2015;13(1):7.

    Article  CAS  Google Scholar 

  92. Zheng G, Zhao R, Xu A, Shen Z, Chen X, Shao J. Co-delivery of sorafenib and siVEGF based on mesoporous silica nanoparticles for ASGPR mediated targeted HCC therapy. Eur J Pharm Sci. 2018;111:492–502.

    Article  CAS  PubMed  Google Scholar 

  93. Zhang C, An T, Wang D, Wan G, Zhang M, Wang H, Zhang S, Li R, Yang X, Wang Y. Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly (β-amino ester)/poly (lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma. J Control Release. 2016;226:193–204.

    Article  CAS  PubMed  Google Scholar 

  94. Xue WJ, Feng Y, Wang F, Guo YB, Li P, Wang L, Liu YF, Wang ZW, Yang YM, Mao QS. Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma. Sci Rep. 2016;6:22149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zhu D, Tao W, Zhang H, Liu G, Wang T, Zhang L, Zeng X, Mei L. Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Acta Biomater. 2016;30:144–54.

    Article  CAS  PubMed  Google Scholar 

  96. Tsend-Ayush A, Zhu X, Ding Y, Yao J, Yin L, Zhou J, Yao J. Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma. Nanotechnology. 2017;28(19):195602.

    Article  PubMed  CAS  Google Scholar 

  97. Chen W, Zou Y, Meng F, Cheng R, Deng C, Feijen J, Zhong Z. Glyco-nanoparticles with sheddable saccharide shells: a unique and potent platform for hepatoma-targeting delivery of anticancer drugs. Biomacromolecules. 2014;15(3):900–7.

    Article  CAS  PubMed  Google Scholar 

  98. Guan M, Zhu QL, Liu Y, Bei YY, Gu ZL, Zhang XN, Zhang Q. Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers. Int J Nanomedicine. 2012;7:1921.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Thapa B, Kumar P, Zeng H, Narain R. Asialoglycoprotein receptor-mediated gene delivery to hepatocytes using galactosylated polymers. Biomacromolecules. 2015;16(9):3008–20.

    Article  CAS  PubMed  Google Scholar 

  100. Liang HF, Chen CT, Chen SC, Kulkarni AR, Chiu YL, Chen MC, Sung HW. Paclitaxel-loaded poly (γ-glutamic acid)-poly (lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials. 2006;27(9):2051–9.

    Article  CAS  PubMed  Google Scholar 

  101. Zhu X, Du Y, Yu R, Liu P, Shi D, Chen Y, Wang Y, Huang F. Galactosylated chitosan oligosaccharide nanoparticles for hepatocellular carcinoma cell-targeted delivery of adenosine triphosphate. Int J Mol Sci. 2013;14(8):15755–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Ding J, Xiao C, Li Y, Cheng Y, Wang N, He C, Zhuang X, Zhu X, Chen X. Efficacious hepatoma-targeted nanomedicine self-assembled from galactopeptide and doxorubicin driven by two-stage physical interactions. J Control Release. 2013;169(3):193–203.

    Article  CAS  PubMed  Google Scholar 

  103. Shi L, Tang C, Yin C. Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma. Biomaterials. 2012;33(30):7594–604.

    Article  CAS  PubMed  Google Scholar 

  104. Chittasupho C, Jaturanpinyo M, Mangmool S. Pectin nanoparticle enhances cytotoxicity of methotrexate against hepG2 cells. Drug Deliv. 2013;20(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  105. Huang L, Wang Y, Ling X, Chaurasiya B, Yang C, Du Y, Tu J, Xiong Y, Sun C. Efficient delivery of paclitaxel into ASGPR over-expressed cancer cells using reversibly stabilized multifunctional pullulan nanoparticles. Carbohydr Polym. 2017;159:178–87.

    Article  CAS  PubMed  Google Scholar 

  106. Pranatharthiharan S, Patel MD, Malshe VC, Pujari V, Gorakshakar A, Madkaikar M, Ghosh K, Devarajan PV. Asialoglycoprotein receptor targeted delivery of doxorubicin nanoparticles for hepatocellular carcinoma. Drug Deliv. 2017;24(1):20–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Jain N, Rajoriya V, Jain PK, Jain AK. Lactosaminated-N-succinyl chitosan nanoparticles for hepatocyte-targeted delivery of acyclovir. J Nanopart Res. 2014;16(1):2136.

    Article  CAS  Google Scholar 

  108. Li X, Wu Q, Chen Z, Gong X, Lin X. Preparation, characterization and controlled release of liver-targeting nanoparticles from the amphiphilic random copolymer. Polymer. 2008;49(22):4769–75.

    Article  CAS  Google Scholar 

  109. Joshi VM, Devarajan PV. Receptor-mediated hepatocyte-targeted delivery of primaquine phosphate nanocarboplex using a carbohydrate ligand. Drug Deliv Transl Res. 2014;4(4):353–64.

    Article  CAS  PubMed  Google Scholar 

  110. Varshosaz J, Hassanzadeh F, Sadeghi H, Khadem M. Galactosylated nanostructured lipid carriers for delivery of 5-FU to hepatocellular carcinoma. J Liposome Res. 2012;22(3):224–36.

    Article  CAS  PubMed  Google Scholar 

  111. Xu Z, Chen L, Gu W, Gao Y, Lin L, Zhang Z, Xi Y, Li Y. The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma. Biomaterials. 2009;30(2):226–32.

    Article  PubMed  CAS  Google Scholar 

  112. Chen S, Tam YY, Lin PJ, Leung AK, Tam YK, Cullis PR. Development of lipid nanoparticle formulations of siRNA for hepatocyte gene silencing following subcutaneous administration. J Control Release. 2014;196:106–12.

    Article  CAS  PubMed  Google Scholar 

  113. Akinc A, Querbes W, De S, Qin J, Frank-Kamenetsky M, Jayaprakash KN, Jayaraman M, Rajeev KG, Cantley WL, Dorkin JR, Butler JS. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol Ther. 2010;18(7):1357–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Oh H, Jo HY, Park J, Kim DE, Cho JY, Kim PH, Kim KS. Galactosylated liposomes for targeted co-delivery of doxorubicin/vimentin siRNA to hepatocellular carcinoma. Nano. 2016;6(8):141.

    Google Scholar 

  115. Zhou X, Zhang M, Bryant Yung HL, Zhou C, Lee LJ, Lee RJ. Lactosylated liposomes for targeted delivery of doxorubicin to hepatocellular carcinoma. Int J Nanomedicine. 2012;7:5465.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Hai L, Zhang ZR, Wang S, Xiao X, Wu Y. Synthesis of multivalent galactosides as targeting ligand for gene delivery. Synth Commun. 2010;40(12):1802–11.

    Article  CAS  Google Scholar 

  117. Sun X, Hai L, Wu Y, Hu HY, Zhang ZR. Targeted gene delivery to hepatoma cells using galactosylated liposome-polycation-DNA complexes (LPD). J Drug Target. 2005;13(2):121–8.

    Article  CAS  PubMed  Google Scholar 

  118. Zhang X, Guo S, Fan R, Yu M, Li F, Zhu C, Gan Y. Dual-functional liposome for tumor targeting and overcoming multidrug resistance in hepatocellular carcinoma cells. Biomaterials. 2012;33(29):7103–14.

    Article  CAS  PubMed  Google Scholar 

  119. Zhang Y, Qi XR, Gao Y, Wei L, Maitani Y, Nagai T. Mechanisms of co-modified liver-targeting liposomes as gene delivery carriers based on cellular uptake and antigens inhibition effect. J Control Release. 2007;117(2):281–90.

    Article  CAS  PubMed  Google Scholar 

  120. Cho HA, Park IS, Kim TW, Oh YK, Yang KS, Kim JS. Suppression of hepatitis B virus-derived human hepatocellular carcinoma by NF-κB-inducing kinase-specific siRNA using liver-targeting liposomes. Arch Pharm Res. 2009;32(7):1077–86.

    Article  CAS  PubMed  Google Scholar 

  121. Suriano F, Pratt R, Tan JP, Wiradharma N, Nelson A, Yang YY, Dubois P, Hedrick JL. Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery. Biomaterials. 2010;31(9):2637–45.

    Article  CAS  PubMed  Google Scholar 

  122. Zhong Y, Yang W, Sun H, Cheng R, Meng F, Deng C, Zhong Z. Ligand-directed reduction-sensitive shell-sheddable biodegradable micelles actively deliver doxorubicin into the nuclei of target cancer cells. Biomacromolecules. 2013;14(10):3723–30.

    Article  CAS  PubMed  Google Scholar 

  123. Liu S, Huang Y, Chen X, Zhang L, Jing X. Lactose mediated liver-targeting effect observed by ex vivo imaging technology. Biomaterials. 2010;31(9):2646–54.

    Article  PubMed  CAS  Google Scholar 

  124. Oishi M, Nagatsugi F, Sasaki S, Nagasaki Y, Kataoka K. Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotides containing acid-labile linkages. Chembiochem. 2005;6(4):718–25.

    Article  CAS  PubMed  Google Scholar 

  125. Zou Y, Song Y, Yang W, Meng F, Liu H, Zhong Z. Galactose-installed photo-crosslinked pH-sensitive degradable micelles for active targeting chemotherapy of hepatocellular carcinoma in mice. J Control Release. 2014;193:154–61.

    Article  CAS  PubMed  Google Scholar 

  126. Yang R, Meng F, Ma S, Huang F, Liu H, Zhong Z. Galactose-decorated cross-linked biodegradable poly (ethylene glycol)-b-poly (ε-caprolactone) block copolymer micelles for enhanced hepatoma-targeting delivery of paclitaxel. Biomacromolecules. 2011;12(8):3047–55.

    Article  CAS  PubMed  Google Scholar 

  127. Craparo EF, Triolo D, Pitarresi G, Giammona G, Cavallaro G. Galactosylated micelles for a ribavirin prodrug targeting to hepatocytes. Biomacromolecules. 2013;14(6):1838–49.

    Article  CAS  PubMed  Google Scholar 

  128. Villa R, Cerroni B, Viganò L, Margheritelli S, Abolafio G, Oddo L, Paradossi G, Zaffaroni N. Targeted doxorubicin delivery by chitosan-galactosylated modified polymer microbubbles to hepatocarcinoma cells. Colloids Surf B: Biointerfaces. 2013;110:434–42.

    Article  CAS  PubMed  Google Scholar 

  129. Wei W, Yue ZG, Qu JB, Yue H, Su ZG, Ma GH. Galactosylated nanocrystallites of insoluble anticancer drug for liver-targeting therapy: an in vitro evaluation. Nanomedicine. 2010;5(4):589–96.

    Article  CAS  PubMed  Google Scholar 

  130. Duan C, Gao J, Zhang D, Jia L, Liu Y, Zheng D, Liu G, Tian X, Wang F, Zhang Q. Galactose-decorated pH-responsive nanogels for hepatoma-targeted delivery of oridonin. Biomacromolecules. 2011;12(12):4335–43.

    Article  CAS  PubMed  Google Scholar 

  131. Managit C, Kawakami S, Yamashita F, Hashida M. Uptake characteristics of galactosylated emulsion by HepG2 hepatoma cells. Int J Pharm. 2005;301(1–2):255–61.

    Article  CAS  PubMed  Google Scholar 

  132. Liu D, Hu H, Zhang J, Zhao X, Tang X, Chen D. Drug pH-sensitive release in vitro and targeting ability of polyamidoamine dendrimer complexes for tumor cells. Chem Pharm Bull. 2011;59(1):63–71.

    Article  CAS  Google Scholar 

  133. Kuruvilla SP, Tiruchinapally G, Crouch AC, ElSayed ME, Greve JM. Dendrimer-doxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model. PLoS One. 2017;12(8):e0181944.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Nasr M, Nafee N, Saad H, Kazem A. Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice. Eur J Pharm Biopharm. 2014;88(1):216–25.

    Article  CAS  PubMed  Google Scholar 

  135. Peng J, Wang K, Tan W, He X, He C, Wu P, Liu F. Identification of live liver cancer cells in a mixed cell system using galactose-conjugated fluorescent nanoparticles. Talanta. 2007;71(2):833–40.

    Article  CAS  PubMed  Google Scholar 

  136. Yang SH, Heo D, Lee E, Kim E, Lim EK, Lee YH, Haam S, Suh JS, Huh YM, Yang J, Park SW. Galactosylated manganese ferrite nanoparticles for targeted MR imaging of asialoglycoprotein receptor. Nanotechnology. 2013;24(47):475103.

    Article  PubMed  CAS  Google Scholar 

  137. Kikkeri R, Lepenies B, Adibekian A, Laurino P, Seeberger PH. In vitro imaging and in vivo liver targeting with carbohydrate capped quantum dots. J Am Chem Soc. 2009;131(6):2110–2.

    Article  CAS  PubMed  Google Scholar 

  138. Ketkar-Atre A, Struys T, Dresselaers T, Hodenius M, Mannaerts I, Ni Y, Lambrichts I, Van Grunsven LA, De Cuyper M, Himmelreich U. In vivo hepatocyte MR imaging using lactose functionalized magnetoliposomes. Biomaterials. 2014;35(3):1015–24.

    Article  CAS  PubMed  Google Scholar 

  139. Kim EM, Jeong HJ, Kim SL, Sohn MH, Nah JW, Bom HS, Park IK, Cho CS. Asialoglycoprotein-receptor-targeted hepatocyte imaging using 99mTc galactosylated chitosan. Nucl Med Biol. 2006;33(4):529–34.

    Article  CAS  PubMed  Google Scholar 

  140. Sasaki N, Shiomi S, Iwata Y, Nishiguchi S, Kuroki T, Kawabe J, Ochi H. Clinical usefulness of scintigraphy with^ 9^ 9^ mTc-galactosyl-human serum albumin for prognosis of cirrhosis of the liver. J Nucl Med. 1999;40(10):1652–6.

    CAS  PubMed  Google Scholar 

  141. Stadalnik RC, Vera DR, Woodle ES, Trudeau WL, Porter BA, Ward RE, Krohn KA, O’Grady LF. Technetium-99m NGA functional hepatic imaging: preliminary clinical experience. J Nucl Med. 1985;26(11):1233–42.

    CAS  PubMed  Google Scholar 

  142. Jeong JM, Hong MK, Lee J, Son M, So Y, Lee DS, Chung JK, Lee MC. 99mTc-neolactosylated human serum albumin for imaging the hepatic asialoglycoprotein receptor. Bioconjug Chem. 2004;15(4):850–5.

    Article  CAS  PubMed  Google Scholar 

  143. Liang J, Zhang X, Miao Y, Li J, Gan Y. Lipid-coated iron oxide nanoparticles for dual-modal imaging of hepatocellular carcinoma. Int J Nanomedicine. 2017;12:2033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Kouda K, Kil Ha-Kawa S, Tanaka Y. Increased technetium-99m-GSA uptake per hepatocyte in rats with administration of dimethylnitrosamine or hepatocyte growth factor. J Nucl Med. 1998;39:1463–7.

    CAS  PubMed  Google Scholar 

  145. Haubner R, Vera DR, Farshchi-Heydari S, Helbok A, Rangger C, Putzer D, Virgolini IJ. Development of 68 Ga-labelled DTPA galactosyl human serum albumin for liver function imaging. Eur J Nucl Med Mol Imaging. 2013;40(8):1245–55.

    Article  CAS  PubMed  Google Scholar 

  146. Song MG, Jang SA, Youn H, Lee YS, Jeong JM, Chung JK, Kratz F, Lee DS, Kang KW. Enhancement of targeting ability of 64Cu-lactosaminated HSA to asialoglycoprotein receptor positive cells by addition of lactosamine residues. J Nucl Med. 2014;55(supplement 1):1046.

    Google Scholar 

  147. Jung Y, Hwang HS, Na K. Galactosylated iodine-based small molecule IV CT contrast agent for bile duct imaging. Biomaterials. 2018;160:15–23.

    Article  CAS  PubMed  Google Scholar 

  148. Yoshinori M, Masaharu M, Yuri H, Sayoko N, Nao S, Makoto H. Molecular imaging contrast media for visualization of liver function. Magn Reson Imaging. 2010;28(5):708–15.

    Article  CAS  PubMed  Google Scholar 

  149. Zhang D, Guo Z, Zhang P, Li Y, Su X, You L, Gao M, Liu C, Wu H, Zhang X. Simplified quantification method for in vivo SPECT/CT imaging of asialoglycoprotein receptor with 99m Tc-p (VLA-co-VNI) to assess and stage hepatic fibrosis in mice. Sci Rep. 2016;6:25377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Wu LJ, Pan YD, Pei XY, Chen H, Nguyen S, Kashyap A, Liu J, Wu J. Capturing circulating tumor cells of hepatocellular carcinoma. Cancer Lett. 2012;326(1):17–22.

    Article  CAS  PubMed  Google Scholar 

  151. Xu W, Cao L, Chen L, Li J, Zhang XF, Qian HH, Kang XY, Zhang Y, Liao J, Shi LH, Yang YF. Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res. 2011;17(11):3783–93.

    Article  PubMed  Google Scholar 

  152. Deal KA, Cristel ME, Welch MJ. Cellular distribution of 111In-LDTPA galactose BSA in normal and asialoglycoprotein receptor-deficient mouse liver. Nucl Med Biol. 1998;25(4):379–85.

    Article  CAS  PubMed  Google Scholar 

  153. Richard C, Chaumet-Riffaud P, Belland A, Parat A, Contino-Pepin C, Bessodes M, Scherman D, Pucci B, Mignet N. Amphiphilic perfluoroalkyl carbohydrates as new tools for liver imaging. Int J Pharm. 2009;379(2):301–8.

    Article  CAS  PubMed  Google Scholar 

  154. Iimuro Y, Kashiwagi T, Yamanaka J, Hirano T, Saito S, Sugimoto T, Watanabe S, Kuroda N, Okada T, Asano Y, Uyama N. Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters. J Hepatobiliary Pancreat Sci. 2010;17(5):673–81.

    Article  PubMed  Google Scholar 

  155. Ogawara KI, Nishikawa M, Takakura Y, Hashida M. Pharmacokinetic analysis of hepatic uptake of galactosylated bovine serum albumin in a perfused rat liver. J Control Release. 1998;50(1–3):309–17.

    Article  CAS  PubMed  Google Scholar 

  156. Ha-Kawa SK, Tanaka Y, Hasebe S, Kuniyasu Y, Koizumi K, Ishii Y, Yamamoto K, Kashiwagi T, Ito A, Kudo M, Ikekubo K. Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: a multicentre study. Eur J Nucl Med. 1997;24(2):130–7.

    Article  CAS  PubMed  Google Scholar 

  157. Vera DR, Stadalnik RC, Metz CE, Pimstone NR. Diagnostic performance of a receptor-binding radiopharmacokinetic model. J Nucl Med. 1996;37(1):160–4.

    CAS  PubMed  Google Scholar 

  158. Sharma A, Kim EJ, Shi H, Lee JY, Chung BG, Kim JS. Development of a theranostic prodrug for colon cancer therapy by combining ligand-targeted delivery and enzyme-stimulated activation. Biomaterials. 2018;155:145–51.

    Article  CAS  PubMed  Google Scholar 

  159. Zeng Y, Zhang D, Wu M, Liu Y, Zhang X, Li L, Li Z, Han X, Wei X, Liu X. Lipid-AuNPs@ PDA nanohybrid for MRI/CT imaging and photothermal therapy of hepatocellular carcinoma. ACS Appl Mater Interfaces. 2014;6(16):14266–77.

    Article  CAS  PubMed  Google Scholar 

  160. Ji DK, Zhang Y, Zang Y, Liu W, Zhang X, Li J, Chen GR, James TD, He XP. Receptor-targeting fluorescence imaging and theranostics using a graphene oxide based supramolecular glycocomposite. J Mater Chem B. 2015;3(47):9182–5.

    Article  CAS  PubMed  Google Scholar 

  161. Quan S, Wang Y, Zhou A, Kumar P, Narain R. Galactose-based thermosensitive nanogels for targeted drug delivery of iodoazomycin arabinofuranoside (IAZA) for theranostic management of hypoxic hepatocellular carcinoma. Biomacromolecules. 2015;16(7):1978–86.

    Article  CAS  PubMed  Google Scholar 

  162. Lee MH, Sessler JL, Kim JS. Disulfide-based multifunctional conjugates for targeted theranostic drug delivery. Acc Chem Res. 2015;48(11):2935–46.

    Article  CAS  PubMed  Google Scholar 

  163. Seymour LW, Ferry DR, Anderson D, Hesslewood S, Julyan PJ, Poyner R, Doran J, Young AM, Burtles S, Kerr DJ. Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. J Clin Oncol. 2002;20(6):1668–76.

    Article  CAS  PubMed  Google Scholar 

  164. Roy M, Finley J, Coskran T, Shen A, Xia S, Thuma B, Mascitti V. Characterization of asialoglycoprotein receptor (ASGPR) directed hepatocellular delivery using a pfizer developed targeting ligand PF-06853291. FASEB J. 2017;31(1_supplement):938–7.

    Google Scholar 

  165. Rajeev KG, Nair JK, Jayaraman M, Charisse K, Taneja N, O’Shea J, Willoughby JL, Yucius K, Nguyen T, Shulga-Morskaya S, Milstein S. Hepatocyte-specific delivery of siRNAs conjugated to novel non-nucleosidic trivalent N-acetylgalactosamine elicits robust gene silencing in vivo. Chembiochem. 2015;16(6):903–8.

    Article  CAS  PubMed  Google Scholar 

  166. Prakash TP, Graham MJ, Yu J, Carty R, Low A, Chappell A, Schmidt K, Zhao C, Aghajan M, Murray HF, Riney S. Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice. Nucleic Acids Res. 2014;42(13):8796–807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. A study of ALN-HBV in healthy adult volunteers and non-cirrhotic patients with chronic hepatitis B virus (HBV) infection [Internet]. NIH. 2016 [cited June 16, 2019]. Available from: https://clinicaltrials.gov/ct2/show/NCT02826018?term=ALN-HBV&rank=1.

  168. Terada T, Iwai M, Kawakami S, Yamashita F, Hashida M. Novel PEG-matrix metalloproteinase-2 cleavable peptide-lipid containing galactosylated liposomes for hepatocellular carcinoma-selective targeting. J Control Release. 2006;111(3):333–42.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, Mumbai, India

    Saugandha Das & Pawan Kudale

  2. Department of Pharmaceutical Sciences, Insitute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence, Government of Maharashtra, Mumbai, India

    Prajakta Dandekar & Padma V. Devarajan

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  1. Saugandha Das
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  3. Prajakta Dandekar
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  1. Department of Pharmaceutical Sciences, Insitute of Chemical Technology Deemed University, Elite Status and Centre of Excellence Government of Maharashtra, Mumbai, India

    Padma V. Devarajan

  2. Department of Pharmaceutical Sciences, Insitute of Chemical Technology Deemed University, Elite Status and Centre of Excellence Government of Maharashtra, Mumbai, India

    Prajakta Dandekar

  3. Piramal Enterprises Limited, Pharmaceutical R&D, Mumbai, India

    Anisha A. D'Souza

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Das, S., Kudale, P., Dandekar, P., Devarajan, P.V. (2019). Asialoglycoprotein Receptor and Targeting Strategies. In: Devarajan, P., Dandekar, P., D'Souza, A. (eds) Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis. AAPS Advances in the Pharmaceutical Sciences Series, vol 39. Springer, Cham. https://doi.org/10.1007/978-3-030-29168-6_12

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