Skip to main content
SpringerLink
Log in

Scavenger Receptor and Targeting Strategies

  • Chapter
  • First Online:
Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis

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

Abstract

Scavenger receptors constitute a group of receptors on the cell surface that attach to various ligands and remove the targets that are non-self or altered. Signaling, transport, endocytosis, phagocytosis, and adhesion resulting in the removal of harmful and degraded substances are some functions of these receptors. Scavenger receptors bind a large repertoire of ligands indicating their involvement in homeostasis and multiple disease pathologies. In this chapter, we describe the role of scavenger receptor group in the pathogenesis of infections and cancer. In addition, we present a variety of ligands with their scavenger receptor binding strategies through different examples of targeted drug delivery systems.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AcLDL:

Acylated low-density lipoprotein

Aco-HSA:

Polyaconitylated-human serum albumin

AGE:

Advanced glycation end products

AgNPs:

Silver nanoparticles

BBB:

Blood–brain barrier

BSA:

Bovine serum albumin

CFUs:

Colony-forming units

CR:

Cysteine rich

CXC:

Chemokine receptor 16

DCP:

Dicetylphosphate

DCs:

Dendritic cells

EDCs:

Endothelial cells

EGF:

Epidermal growth factor

Fe2O3:

Iron oxide

FEEL:

Fasciclin EGF-like, and lamin-type EGF-like domains

GPI:

Glycosyl-phosphatidylinositol

HDL:

High-density lipoprotein

Hsp:

Heat shock proteins

LAMP:

Lysosome-associated membrane glycoprotein

LCO:

Lithocholic oleate

LDL:

Low-density lipoprotein

LDLR:

Low-density lipoprotein receptor

LOX-1:

Lectin-like oxidized LDL receptor-1

LPS:

Lipopolysaccharide

LTA:

Lipoteichoic acid

MARCO:

Macrophage receptor with collagenous structure

MBSA:

Maleylated albumin

MTX:

Methotrexate

NMs:

Nanomedicines

NK cells:

Natural Killer cells

OxLDL:

Oxidized low-density lipoprotein

PAS:

p-amino salicylic acid

PC:

Phosphatidylcholine

PG:

Phosphatidylglycerol

POPC:

Palmitoyloleoyl-phosphatidylcholine

PS:

Phosphatidylserine

RBCs:

Red blood cells

ROS:

Reactive oxygen species

S1-CLP:

Stabilin-1 interacting chitinase-like protein

SCARA-5:

Scavenger receptor class A member 5

SiRNA:

Small interfering ribonucleic acid

SNP:

Single nucleotide polymorphism

SPARC:

Secreted protein acidic and rich in cysteine

SR:

Scavenger receptor

SRCL:

Scavenger receptors with C-type lectin

SRPSOX:

Scavenger receptor that binds phosphatidylserine and oxidized lipids

TAMs:

Tumor-associated macrophages

TiO2:

Titanium dioxide

UGPR:

Uteroglobin-related protein

VLDL:

Very low-density lipoproteins

ZnO:

Zinc oxide

References

  1. Canton J, Neculai D, Grinstein S. Scavenger receptors in homeostasis and immunity. Nat Rev Immunol. 2013;13(9):621–34.

    Article  CAS  PubMed  Google Scholar 

  2. Brown MS, Goldstein JL. Receptor-mediated endocytosis: insights from the lipoprotein receptor system. Proc Natl Acad Sci. 1979;76(7):3330–7.

    Article  CAS  PubMed  Google Scholar 

  3. Brown MS, Goldstein JL, Krieger M, Ho YK, Anderson RG. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J Cell Biol. 1979;82(3):597–613.

    Article  CAS  PubMed  Google Scholar 

  4. Su T, Zhao L, Ruan X, Zuo G, Gong J. Synergistic effect of scavenger receptor A and low-density lipoprotein receptor on macrophage foam cell formation under inflammatory stress. Mol Med Rep. 2013;7(1):37–42.

    Article  CAS  PubMed  Google Scholar 

  5. PrabhuDas MR, Baldwin CL, Bollyky PL, Bowdish DM, Drickamer K, Febbraio M, Herz J, Kobzik L, Krieger M, Loike J, McVicker B. A consensus definitive classification of scavenger receptors and their roles in health and disease. J Immunol. 2017;198(10):3775–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zani I, Stephen S, Mughal N, Russell D, Homer-Vanniasinkam S, Wheatcroft S, Ponnambalam S. Scavenger receptor structure and function in health and disease. Cell. 2015;4(2):178–201.

    Article  CAS  Google Scholar 

  7. Ashraf MZ, Sahu A. Scavenger receptors: a key player in cardiovascular diseases. Biomol Concepts. 2012;3(4):371–80.

    Article  CAS  PubMed  Google Scholar 

  8. de Winther MP, van Dijk KW, Havekes LM, Hofker MH. Macrophage scavenger receptor class A: a multifunctional receptor in atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;20(2):290–7.

    Article  PubMed  Google Scholar 

  9. Wada Y, Doi T, Matsumoto A, Asaoka H, Honda M, Hatano H, Emi M, Naito M, Mori T, Takahashi K, Nakamura H. Structure and function of macrophage scavenger receptors. Ann N Y Acad Sci. 1994;748(1):226–38.

    Article  Google Scholar 

  10. Bowdish DM, Gordon S. Conserved domains of the class A scavenger receptors: evolution and function. Immunol Rev. 2009;227(1):19–31.

    Article  CAS  PubMed  Google Scholar 

  11. Resnick D, Chatterton JE, Schwartz K, Slayter H, Krieger M. Structures of class A macrophage scavenger receptors electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain. J Biol Chem. 1996;271(43):26924–30.

    Article  CAS  PubMed  Google Scholar 

  12. Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M. Type I macrophage scavenger receptor contains α-helical and collagen-like coiled coils. Nature. 1990;343(6258):531–5.

    Article  CAS  PubMed  Google Scholar 

  13. Elomaa O, Sankala M, Pikkarainen T, Bergmann U, Tuuttila A, Raatikainen-Ahokas A, Sariola H, Tryggvason K. Structure of the human macrophage MARCO receptor and characterization of its bacteria-binding region. J Biol Chem. 1998;273(8):4530–8.

    Article  CAS  PubMed  Google Scholar 

  14. Jiang Y, Oliver P, Davies KE, Platt N. Identification and characterization of murine SCARA5, a novel class A scavenger receptor that is expressed by populations of epithelial cells. J Biol Chem. 2006;281(17):11834–45.

    Article  CAS  PubMed  Google Scholar 

  15. Nakamura K, Funakoshi H, Tokunaga F, Nakamura T. Molecular cloning of a mouse scavenger receptor with C-type lectin (SRCL), a novel member of the scavenger receptor family. Biochim Biophys Acta. 2001;1522(1):53–8.

    Article  CAS  PubMed  Google Scholar 

  16. Thorne RF, Meldrum CJ, Harris SJ, Dorahy DJ, Shafren DR, Berndt MC, Burns GF, Gibson PG. CD36 forms covalently associated dimers and multimers in platelets and transfected COS-7 cells. Biochem Biophys Res Commun. 1997;240(3):812–8.

    Article  CAS  PubMed  Google Scholar 

  17. Reaven E, Cortez Y, Leers-Sucheta S, Nomoto A, Azhar S. Dimerization of the scavenger receptor class B type I formation, function, and localization in diverse cells and tissues. J Lipid Res. 2004;45(3):513–28.

    Article  CAS  PubMed  Google Scholar 

  18. Pearson A, Lux AL, Krieger M. Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor from Drosophila melanogaster. Proc Natl Acad Sci. 1995;92(9):4056–60.

    Article  CAS  PubMed  Google Scholar 

  19. Jiang Z, Shih DM, Xia YR, Lusis AJ, de Beer FC, de Villiers WJ, van der Westhuyzen DR, de Beer MC. Structure, organization, and chromosomal mapping of the gene encoding macrosialin, a macrophage-restricted protein. Genomics. 1998;50(2):199–205.

    Article  CAS  PubMed  Google Scholar 

  20. Yamanaka S, Zhang XY, Miura K, Kim S, Iwao H. The human gene encoding the lectin-type oxidized LDL receptor (OLR1) is a novel member of the natural killer gene complex with a unique expression profile. Genomics. 1998;54(2):191–9.

    Article  CAS  PubMed  Google Scholar 

  21. Ishii J, Adachi H, Aoki J, Koizumi H, Tomita S, Suzuki T, Tsujimoto M, Inoue K, Arai H. SREC-II, a new member of the scavenger receptor type F family, trans-interacts with SREC-I through its extracellular domain. J Biol Chem. 2002;277(42):39696–702.

    Article  CAS  PubMed  Google Scholar 

  22. Adachi H, Tsujimoto M. FEEL-1, a novel scavenger receptor with in vitro bacteria-binding and angiogenesis-modulating activities. J Biol Chem. 2002;277(37):34264–70.

    Article  CAS  PubMed  Google Scholar 

  23. Rodamilans B, Muñoz IG, Bragado-Nilsson E, Sarrias MR, Padilla O, Blanco FJ, Lozano F, Montoya G. Crystal structure of the third extracellular domain of CD5 reveals the fold of a group B scavenger cysteine-rich receptor domain. J Biol Chem. 2007;282(17):12669–77.

    Article  CAS  PubMed  Google Scholar 

  24. Ibrahim ZA, Armour CL, Phipps S, Sukkar MB. RAGE and TLRs: relatives, friends or neighbours. Mol Immunol. 2013;56(4):739–44.

    Article  CAS  PubMed  Google Scholar 

  25. Naor D, Sionov RV, Ish-Shalom D. CD44: structure, function and association with the malignant process. Adv Cancer Res. 1997;71:241–319. Academic Press.

    Article  CAS  PubMed  Google Scholar 

  26. Dzwonek J, Wilczynski GM. CD44: molecular interactions, signaling and functions in the nervous system. Front Cell Neurosci. 2015;9:175.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Oh SJ, Kim TH, Lim JM, Jeong JW. Progesterone induces expression of Lrp2 in the murine uterus. Biochem Biophys Res Commun. 2013;441(1):175–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bartolome F, Antequera D, Tavares E, Pascual C, Maldonado R, Camins A, Carro E. Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin. J Neuroinflammation. 2017;14(1):26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Plüddemann A, Neyen C, Gordon S. Macrophage scavenger receptors and host-derived ligands. Methods. 2007;43(3):207–17.

    Article  PubMed  CAS  Google Scholar 

  30. Ashkenas J, Penman M, Vasile E, Acton S, Freeman M, Krieger M. Structures and high and low affinity ligand binding properties of murine type I and type II macrophage scavenger receptors. J Lipid Res. 1993;34(6):983–1000.

    CAS  PubMed  Google Scholar 

  31. Stephen SL, Freestone K, Dunn S, Twigg MW, Homer-Vanniasinkam S, Walker JH, Wheatcroft SB, Ponnambalam S. Scavenger receptors and their potential as therapeutic targets in the treatment of cardiovascular disease. Int J Hypertens. 2010;2010:646929.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Ojala JR, Pikkarainen T, Tuuttila A, Sandalova T, Tryggvason K. Crystal structure of the cysteine-rich domain of scavenger receptor MARCO reveals the presence of a basic and an acidic cluster that both contribute to ligand recognition. J Biol Chem. 2007;282(22):16654–66.

    Article  CAS  PubMed  Google Scholar 

  33. Chao Y, Makale M, Karmali PP, Sharikov Y, Tsigelny I, Merkulov S, Kesari S, Wrasidlo W, Ruoslahti E, Simberg D. Recognition of dextran–superparamagnetic iron oxide nanoparticle conjugates (Feridex) via macrophage scavenger receptor charged domains. Bioconjug Chem. 2012;23(5):1003–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ibrahimi A, Abumrad NA. Role of CD36 in membrane transport of long-chain fatty acids. Curr Opin Clin Nutr Metab Care. 2002;5(2):139–45.

    Article  CAS  PubMed  Google Scholar 

  35. Chen Y, Wang X, Ben J, Yue S, Bai H, Guan X, Bai X, Jiang L, Ji Y, Fan L, Chen Q. The di-leucine motif contributes to class a scavenger receptor-mediated internalization of acetylated lipoproteins. Arterioscler Thromb Vasc Biol. 2006;26(6):1317–22.

    Article  CAS  PubMed  Google Scholar 

  36. Murphy JE, Vohra RS, Dunn S, Holloway ZG, Monaco AP, Homer-Vanniasinkam S, Walker JH, Ponnambalam S. Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. J Cell Sci. 2008;121(13):2136–47.

    Article  CAS  PubMed  Google Scholar 

  37. Zeng Y, Tao N, Chung KN, Heuser JE, Lublin DM. Endocytosis of oxidized low density lipoprotein through scavenger receptor CD36 utilizes a lipid raft pathway that does not require caveolin-1. J Biol Chem. 2003;278(46):45931–6.

    Article  CAS  PubMed  Google Scholar 

  38. Rahaman SO, Lennon DJ, Febbraio M, Podrez EA, Hazen SL, Silverstein RL. A CD36-dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metab. 2006;4(3):211–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hughes DA, Fraser IP, Gordon S. Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs. Eur J Immunol. 1995;25(2):466–73.

    Article  CAS  PubMed  Google Scholar 

  40. Zingg JM, Ricciarelli R, Azzi A. Scavenger receptors and modified lipoproteins: fatal attractions. IUBMB Life. 2000;49(5):397–403.

    Article  CAS  PubMed  Google Scholar 

  41. Platt N, Gordon S. Scavenger receptors: diverse activities and promiscuous binding of polyanionic ligands. Chem Biol. 1998;5(8):R 193–203.

    Article  CAS  Google Scholar 

  42. Elomaa O, Kangas M, Sahlberg C, Tuukkanen J, Sormunen R, Liakka A, Thesleff I, Kraal G, Tryggvason K. Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. Cell. 1995;80(4):603–9.

    Article  CAS  PubMed  Google Scholar 

  43. Terpstra V, van Amersfoort ES, van Velzen AG, Kuiper J, van Berkel TJ. Hepatic and extrahepatic scavenger receptors: function in relation to disease. Arterioscler Thromb Vasc Biol. 2000;20(8):1860–72.

    Article  CAS  PubMed  Google Scholar 

  44. Rämet M, Pearson A, Manfruelli P, Li X, Koziel H, Göbel V, Chung E, Krieger M, Ezekowitz RA. Drosophila scavenger receptor CI is a pattern recognition receptor for bacteria. Immunity. 2001;15(6):1027–38.

    Article  PubMed  Google Scholar 

  45. Ramprasad MP, Terpstra V, Kondratenko N, Quehenberger O, Steinberg D. Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein. Proc Natl Acad Sci. 1996;93(25):14833–8.

    Article  CAS  PubMed  Google Scholar 

  46. Moriwaki H, Kume N, Sawamura T, Aoyama T, Hoshikawa H, Ochi H, Nishi E, Masaki T, Kita T. Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein. Arterioscler Thromb Vasc Biol. 1998;18(10):1541–7.

    Article  CAS  PubMed  Google Scholar 

  47. Berwin B, Delneste Y, Lovingood RV, Post SR, Pizzo SV. SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin. J Biol Chem. 2004;279(49):51250–7.

    Article  CAS  PubMed  Google Scholar 

  48. Shimaoka T, Kume N, Minami M, Hayashida K, Kataoka H, Kita T, Yonehara S. Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages. J Biol Chem. 2000;275(52):40663–6.

    Article  CAS  PubMed  Google Scholar 

  49. Prevo R, Banerji S, Ni J, Jackson DG. Rapid plasma membrane-endosomal trafficking of the lymph node sinus and high endothelial venule scavenger receptor/homing receptor stabilin-1 (FEEL-1/CLEVER-1). J Biol Chem. 2004;279(50):52580–92.

    Article  CAS  PubMed  Google Scholar 

  50. Vasquez M, Simões I, Consuegra-Fernández M, Aranda F, Lozano F, Berraondo P. Exploiting scavenger receptors in cancer immunotherapy: lessons from CD5 and SR-B1. Eur J Immunol. 2017;47(7):1108–18.

    Article  CAS  PubMed  Google Scholar 

  51. Yu X, Guo C, Fisher PB, Subjeck JR, Wang XY. Scavenger receptors: emerging roles in cancer biology and immunology. Adv Cancer Res. 2015;128:309–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Danilo C, Gutierrez-Pajares JL, Mainieri MA, Mercier I, Lisanti MP, Frank PG. Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development. Breast Cancer Res. 2013;15(5):R87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Twiddy AL, Cox ME, Wasan KM. Knockdown of scavenger receptor class B type I reduces prostate specific antigen secretion and viability of prostate cancer cells. Prostate. 2012;72(9):955–65.

    Article  CAS  PubMed  Google Scholar 

  54. Kamada N, Kodama T, Suzuki H. Macrophage scavenger receptor (SR-A I/II) deficiency reduced diet-induced atherosclerosis in C57BL/6J mice. J Atheroscler Thromb. 2001;8(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  55. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science. 1996;271(5248):518–20.

    Article  CAS  PubMed  Google Scholar 

  56. Husemann J, Loike JD, Anankov R, Febbraio M, Silverstein SC. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia. 2002;40(2):195–205.

    Article  PubMed  Google Scholar 

  57. Terpstra V, Bird DA, Steinberg D. Evidence that the lipid moiety of oxidized low density lipoprotein plays a role in its interaction with macrophage receptors. Proc Natl Acad Sci. 1998;95(4):1806–11.

    Article  CAS  PubMed  Google Scholar 

  58. El Khoury J, Hickman SE, Thomas CA, Cao L, Silverstein SC, Loike JD. Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils. Nature. 1996;382(6593):716–9.

    Article  PubMed  Google Scholar 

  59. Dunne DW, Resnick D, Greenberg J, Krieger M, Joiner KA. The type I macrophage scavenger receptor binds to gram-positive bacteria and recognizes lipoteichoic acid. Proc Natl Acad Sci. 1994;91(5):1863–7.

    Article  CAS  PubMed  Google Scholar 

  60. Fujiwara M, Baldeschwieler JD, Grubbs RH. Receptor-mediated endocytosis of poly (acrylic acid)-conjugated liposomes by macrophages. Biochim Biophys Acta. 1996;1278(1):59–67.

    Article  PubMed  Google Scholar 

  61. Cordes T, Michelucci A, Hiller K. Itaconic acid: the surprising role of an industrial compound as a mammalian antimicrobial metabolite. Annu Rev Nutr. 2015;35:451–73.

    Article  CAS  PubMed  Google Scholar 

  62. Wang G, Simberg D. Role of scavenger receptors in immune recognition and targeting of nanoparticles. Rev Cell Biol Mol Med. 2006;1(3):166–89.

    Google Scholar 

  63. Minami M, Kume N, Shimaoka T, Kataoka H, Hayashida K, Yonehara S, Kita T. Expression of scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) in human atheroma. Ann N Y Acad Sci. 2001;947(1):373–6.

    Article  CAS  PubMed  Google Scholar 

  64. Gu BJ, Saunders BM, Petrou S, Wiley JS. P2X7 is a scavenger receptor for apoptotic cells in the absence of its ligand, extracellular ATP. J Immunol. 2011;187(5):2365–75.

    Article  CAS  PubMed  Google Scholar 

  65. Podrez EA, Poliakov E, Shen Z, Zhang R, Deng Y, Sun M, Finton PJ, Shan L, Gugiu B, Fox PL, Hoff HF. Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36. J Biol Chem. 2002;277(41):38503–16.

    Article  CAS  PubMed  Google Scholar 

  66. Balasubramanian K, Maeda A, Lee JS, Mohammadyani D, Dar HH, Jiang JF, Croix CM, Watkins S, Tyurin VA, Tyurina YY, Klöditz K. Dichotomous roles for externalized cardiolipin in extracellular signaling: promotion of phagocytosis and attenuation of innate immunity. Sci Signal. 2015;8(395):ra95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Tsubamotoa Y, Yamada N, Watanabe Y, Inaba T, Shiomi M, Shimano H, Gotoda T, Harada K, Shimada M, Ohsuga JI, Kawamura M. Dextran sulfate, a competitive inhibitor for scavenger receptor, prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. Atherosclerosis. 1994;106(1):43–50.

    Article  Google Scholar 

  68. Brown MS, Goldstein JL. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52(1):223–61.

    Article  CAS  PubMed  Google Scholar 

  69. Urano K, Haba M, Yuasa H, Watanabe J. Internalization of fractionated 3H-heparin by the scavenger-like receptor in rat liver parenchymal cells in primary culture. Drug Deliv. 1997;4(3):181–5.

    Article  CAS  Google Scholar 

  70. Harris EN. Heparin clearance by liver scavenger receptors. Biochem Anal Biochem. 2012;1:e114.

    Article  Google Scholar 

  71. Funderburgh JL, Mitschler RR, Funderburgh ML, Roth MR, Chapes SK, Conrad GW. Macrophage receptors for lumican. A corneal keratan sulfate proteoglycan. Invest Ophthalmol Vis Sci. 1997;38(6):1159–67.

    CAS  PubMed  Google Scholar 

  72. Harris EN, Weigel PH. The ligand-binding profile of HARE: hyaluronan and chondroitin sulfates A, C, and D bind to overlapping sites distinct from the sites for heparin, acetylated low-density lipoprotein, dermatan sulfate, and CS-E. Glycobiology. 2008;18(8):638–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sobal G, Sinzinger H. Binding of [99mTc] chondroitin sulfate to scavenger receptors on human chondrocytes as compared to binding of oxidized [125I] LDL on human macrophages. J Recept Sig Transd. 2002;22(1–4):459–70.

    Article  CAS  Google Scholar 

  74. Fang W, Bi D, Zheng R, Cai N, Xu H, Zhou R, Lu J, Wan M, Xu X. Identification and activation of TLR4-mediated signaling pathways by alginate-derived guluronate oligosaccharide in RAW264. 7 macrophages. Sci Rep. 2017;7(1):1663.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. McCourt PA, Smedsrød BH, Melkko J, Johansson S. Characterization of a hyaluronan receptor on rat sinusoidal liver endothelial cells and its functional relationship to scavenger receptors. Hepatology. 1999;30(5):1276–86.

    Article  CAS  PubMed  Google Scholar 

  76. Kelley JL, Ozment TR, Li C, Schweitzer JB, Williams DL. Scavenger receptor-A (CD204): a two-edged sword in health and disease. Crit Rev Immunol. 2014;34(3):241–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Harada M, Imai J, Okuno S, Suzuki T. Macrophage-mediated activation of camptothecin analogue T-2513–carboxymethyl dextran conjugate (T-0128): possible cellular mechanism for antitumor activity. J Control Release. 2000;69(3):389–97.

    Article  CAS  PubMed  Google Scholar 

  78. Tokuda H, Masuda S, Takakura Y, Sezaki H, Hashida M. Specific uptake of succinylated proteins via a scavenger receptor-mediated mechanism in cultured brain microvessel endothelial cells. Biochem Biophys Res Commun. 1993;196(1):18–24.

    Article  CAS  PubMed  Google Scholar 

  79. Hoang B, Ernsting MJ, Roy A, Murakami M, Undzys E, Li SD. Docetaxel-carboxymethylcellulose nanoparticles target cells via a SPARC and albumin dependent mechanism. Biomaterials. 2015;59:66–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Martino JV, Van Limbergen J, Cahill LE. The role of carrageenan and carboxymethylcellulose in the development of intestinal inflammation. Front Pediatr. 2017;5:96.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Iesaki T, Takeuchi T, Okano M, Hashimoto R, Kakigi R, Ishii Y, Okada T. Fucoidan, a ligand of scavenger receptor class a, causes vascular relaxation through a nitric oxide/cGMP-mediated pathway in rat aorta. Atherosclerosis. 2014;235(2):e36.

    Article  Google Scholar 

  82. Thelen T, Hao Y, Medeiros AI, Curtis JL, Serezani CH, Kobzik L, Harris LH, Aronoff DM. The class A scavenger receptor, macrophage receptor with collagenous structure, is the major phagocytic receptor for Clostridium sordellii expressed by human decidual macrophages. J Immunol. 2010;185(7):4328–35.

    Article  CAS  PubMed  Google Scholar 

  83. Rost MS, Sumanas S. Hyaluronic acid receptor stabilin-2 regulates Erk phosphorylation and arterial-venous differentiation in zebrafish. PLoS One. 2014;9(2):e88614.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Marshall-Clarke S, Downes JE, Haga IR, Bowie AG, Borrow P, Pennock JL, Grencis RK, Rothwell P. Polyinosinic acid is a ligand for toll-like receptor 3. J Biol Chem. 2007;282(34):24759–66.

    Article  CAS  PubMed  Google Scholar 

  85. Pearson AM, Rich A, Krieger M. Polynucleotide binding to macrophage scavenger receptors depends on the formation of base-quartet-stabilized four-stranded helices. J Biol Chem. 1993;268(5):3546–54.

    CAS  PubMed  Google Scholar 

  86. Zeng J, Zhang Y, Hao J, Sun Y, Liu S, Bernlohr DA, Sauter ER, Cleary MP, Suttles J, Li B. Stearic acid induces CD11c expression in proinflammatory macrophages via epidermal fatty acid binding protein. J Immunol. 2018;200(10):3407–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Loison C, Mendy F, Sérougne C, Lutton C. Dietary myristic acid modifies the HDL-cholesterol concentration and liver scavenger receptor BI expression in the hamster. Br J Nutr. 2002;87(3):199–210.

    Article  CAS  PubMed  Google Scholar 

  88. Chao Y, Karmali PP, Mukthavaram R, Kesari S, Kouznetsova VL, Tsigelny IF, Simberg D. Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI. ACS Nano. 2013;7(5):4289–98.

    Article  CAS  PubMed  Google Scholar 

  89. Suzuki Y, Tada-Oikawa S, Ichihara G, Yabata M, Izuoka K, Suzuki M, Sakai K, Ichihara S. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation. Toxicol Appl Pharmacol. 2014;278(1):16–25.

    Article  CAS  PubMed  Google Scholar 

  90. Iyer R, Hamilton RF, Li L, Holian A. Silica-induced apoptosis mediated via scavenger receptor in human alveolar macrophages. Toxicol Appl Pharmacol. 1996;141(1):84–92.

    Article  CAS  PubMed  Google Scholar 

  91. Murthy S, Larson-Casey JL, Ryan AJ, He C, Kobzik L, Carter AB. Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure. FASEB J. 2015;29(8):3527–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Resnick D, Freedman NJ, Xu SH, Krieger M. Secreted extracellular domains of macrophage scavenger receptors form elongated trimers which specifically bind crocidolite asbestos. J Biol Chem. 1993;268(5):3538–45.

    CAS  PubMed  Google Scholar 

  93. BEPPU M, HORA M, KIKUGAWA K. A simple method for the assessment of macrophage scavenger receptor-ligand interaction: adherence of erythrocytes coated with oxidized low density lipoprotein and modified albumin to macrophages. Biol Pharm Bull. 1994;17(1):39–46.

    Article  CAS  PubMed  Google Scholar 

  94. Takata K, Horiuchi S, Morino Y. Scavenger receptor-mediated recognition of maleylated albumin and its relation to subsequent endocytic degradation. Biochim Biophys Acta. 1989;984(3):273–80.

    Article  CAS  PubMed  Google Scholar 

  95. Greaves DR, Gordon S. The macrophage scavenger receptor at 30 years of age: current knowledge and future challenges. J Lipid Res. 2009;50(Supplement):S282–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Herrmann M, Schäfer C, Heiss A, Gräber S, Kinkeldey A, Büscher A, Schmitt MM, Bornemann J, Nimmerjahn F, Herrmann M, Helming L. Clearance of fetuin-A–containing calciprotein particles is mediated by scavenger receptor -A. Circ Res. 2012;111(5):575–84.

    Article  CAS  PubMed  Google Scholar 

  97. Melkko J, Hellevik T, Risteli L, Risteli J, Smedsrød B. Clearance of NH2-terminal propeptides of types I and III procollagen is a physiological function of the scavenger receptor in liver endothelial cells. J Exp Med. 1994;179(2):405–12.

    Article  CAS  PubMed  Google Scholar 

  98. Facciponte JG, Wang XY, Subjeck JR. Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A and scavenger receptor expressed by endothelial cells -I. Eur J Immunol. 2007;37(8):2268–79.

    Article  CAS  PubMed  Google Scholar 

  99. Ben J, Zhang Y, Zhou R, Zhang H, Zhu X, Li X, Zhang H, Li N, Zhou X, Bai H, Yang Q. Major vault protein regulates class A scavenger receptor-mediated tumor necrosis factor-α synthesis and apoptosis in macrophages. J Biol Chem. 2013;288(27):20076–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Takahashi T, Suzuki T. Role of sulfatide in normal and pathological cells and tissues. J Lipid Res. 2012;53(8):1437–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Shannahan JH, Bai W, Brown JM. Implications of scavenger receptors in the safe development of nanotherapeutics. Recept Clin Invest. 2015;2(3):e811.

    Google Scholar 

  102. Basu SK, Majumdar S, Mukhopadhyay B, Mukhopadhyay A. Receptor-mediated drug delivery to macrophages. Proc Indian Natl Sci Acad Part B. 1994;60:345–56.

    Google Scholar 

  103. Scherphof GL, Kamps JA. Receptor versus non-receptor mediated clearance of liposomes. Adv Drug Deliv Rev. 1998;32(1–2):81–97.

    Article  CAS  PubMed  Google Scholar 

  104. Semple SC, Chonn A, Cullis PR. Interactions of liposomes and lipid-based carrier systems with blood proteins: relation to clearance behaviour in vivo. Adv Drug Deliv Rev. 1998;32(1–2):3–17.

    Article  CAS  PubMed  Google Scholar 

  105. Liu D, Liu F, Song YK. Recognition and clearance of liposomes containing phosphatidylserine are mediated by serum opsonin. Biochim Biophys Acta. 1995;1235(1):140–6.

    Article  PubMed  Google Scholar 

  106. Devine DV, Wong K, Serrano K, Chonn A, Cullis PR. Liposome complement interactions in rat serum: implications for liposome survival studies. Biochim Biophys Acta. 1994;1191(1):43–51.

    Article  CAS  PubMed  Google Scholar 

  107. Fidler IJ, Raz A, Fogler WE, Kirsh R, Bugelski P, Poste G. Design of liposomes to improve delivery of macrophage-augmenting agents to alveolar macrophages. Cancer Res. 1980;40(12):4460–6.

    CAS  PubMed  Google Scholar 

  108. Chonn A, Semple SC, Cullis PR. Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes. J Biol Chem. 1992;267(26):18759–65.

    CAS  PubMed  Google Scholar 

  109. Vyas SP, Kannan ME, Jain S, Mishra V, Singh P. Design of liposomal aerosols for improved delivery of rifampicin to alveolar macrophages. Int J Pharm. 2004;269(1):37–49.

    Article  CAS  PubMed  Google Scholar 

  110. Kamps JA, Morselt HW, Swart PJ, Meijer DK, Scherphof GL. Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells. Proc Natl Acad Sci. 1997;94(21):11681–5.

    Article  CAS  PubMed  Google Scholar 

  111. Etzerodt A, Maniecki MB, Graversen JH, Møller HJ, Torchilin VP, Moestrup SK. Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163. J Control Release. 2012;160(1):72–80.

    Article  CAS  PubMed  Google Scholar 

  112. Li X, Kan HY, Lavrentiadou S, Krieger M, Zannis V. Reconstituted discoidal ApoE-phospholipid particles are ligands for the scavenger receptor BI The amino-terminal 1–165 domain of ApoE suffices for receptor binding. J Biol Chem. 2002;277(24):21149–57.

    Article  CAS  PubMed  Google Scholar 

  113. Sakai-Kato K, Sakurai M, Takechi-Haraya Y, Nanjo K, Goda Y. Involvement of scavenger receptor class B type 1 and low-density lipoprotein receptor in the internalization of liposomes into HepG2 cells. Biochim Biophys Acta. 2017;1859(11):2253–8.

    Article  CAS  Google Scholar 

  114. Lee KD, Pitas RE, Papahadjopoulos D. Evidence that the scavenger receptor is not involved in the uptake of negatively charged liposomes by cells. Biochim Biophys Acta. 1992;1111(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  115. Pinheiro M, Lúcio M, Lima JL, Reis S. Liposomes as drug delivery systems for the treatment of TB. Nanomedicine. 2011;6(8):1413–28.

    Article  CAS  PubMed  Google Scholar 

  116. Labana S, Pandey R, Sharma S, Khuller GK. Chemotherapeutic activity against murine tuberculosis of once weekly administered drugs (isoniazid and rifampicin) encapsulated in liposomes. Int J Antimicrob Agents. 2002;20(4):301–4.

    Article  CAS  PubMed  Google Scholar 

  117. Pollock S, Nichita NB, Böhmer A, Radulescu C, Dwek RA, Zitzmann N. Polyunsaturated liposomes are antiviral against hepatitis B and C viruses and HIV by decreasing cholesterol levels in infected cells. Proc Natl Acad Sci. 2010;107(40):17176–81.

    Article  CAS  PubMed  Google Scholar 

  118. Tempone AG, Perez D, Rath S, Vilarinho AL, Mortara RA, de Andrade Jr HF. Targeting Leishmania (L.) chagasi amastigotes through macrophage scavenger receptors: the use of drugs entrapped in liposomes containing phosphatidylserine. J Antimicrob Chemother. 2004;54(1):60–8.

    Article  CAS  PubMed  Google Scholar 

  119. da Costa-Silva TA, Galisteo AJ, Lindoso JA, Barbosa LR, Tempone AG. Nanoliposomal buparvaquone immunomodulates Leishmania infantum-infected macrophages and is highly effective in a murine model. Antimicrob Agents Chemother. 2017;61(4):e02297–16.

    PubMed  PubMed Central  Google Scholar 

  120. Pollock S, Antrobus R, Newton L, Kampa B, Rossa J, Latham S, Nichita NB, Dwek RA, Zitzmann N. Uptake and trafficking of liposomes to the endoplasmic reticulum. FASEB J. 2010;24(6):1866–78.

    Article  CAS  PubMed  Google Scholar 

  121. Di Y, Wasan EK, Cawthray J, Wasan KM. Scavenger receptor class BI (SR-BI) mediates uptake of CPX-351 into K562 leukemia cells. Drug Dev Ind Pharm. 2019;45(1):21–6.

    Article  CAS  PubMed  Google Scholar 

  122. Pont I, Calatayud-Pascual A, López-Castellano A, Albelda EP, García-España E, Martí-Bonmatí L, Frias JC, Albelda MT. Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice. PLoS One. 2018;13(1):e0190540.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Rensen PC, Gras JC, Lindfors EK, van Dijk KW, Jukema JW, van Berkel TJ, Biessen EA. Selective targeting of liposomes to macrophages using a ligand with high affinity for the macrophage scavenger receptor class A. Curr Drug Discov Technol. 2006;3(2):135–44.

    Article  CAS  PubMed  Google Scholar 

  124. Gan C, Wang K, Tang Q, Chen Y. Comparative investigation on the sizes and scavenger receptor binding of human native and modified lipoprotein particles with atomic force microscopy. J Nanobiotechnol. 2018;16(1):25.

    Article  CAS  Google Scholar 

  125. Zhang X, Huang G. Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery. Drug Deliv. 2017;24(2):16–21.

    Article  CAS  PubMed  Google Scholar 

  126. Shaw JM, Futch WS, Schook LB. Induction of macrophage antitumor activity by acetylated low density lipoprotein containing lipophilic muramyl tripeptide. Proc Natl Acad Sci. 1988;85(16):6112–6.

    Article  CAS  PubMed  Google Scholar 

  127. Kreuter J, Hekmatara T, Dreis S, Vogel T, Gelperina S, Langer K. Covalent attachment of apolipoprotein AI and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain. J Control Release. 2007;118(1):54–8.

    Article  CAS  PubMed  Google Scholar 

  128. Singh RP, Ramarao P. Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles. Toxicol Lett. 2012;213(2):249–59.

    Article  CAS  PubMed  Google Scholar 

  129. Shannahan JH, Podila R, Aldossari AA, Emerson H, Powell BA, Ke PC, Rao AM, Brown JM. Formation of a protein corona on silver nanoparticles mediates cellular toxicity via scavenger receptors. Toxicol Sci. 2014;143(1):136–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Aldossari AA, Shannahan JH, Podila R, Brown JM. Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation. J Nanopart Res. 2015;17(7):313.

    Article  CAS  Google Scholar 

  131. Lipinski MJ, Frias JC, Amirbekian V, Briley-Saebo KC, Mani V, Samber D, Abbate A, Aguinaldo JG, Massey D, Fuster V, Vetrovec GW. Macrophage-specific lipid-based nanoparticles improve mri detection and characterization of human atherosclerosis. J Am Coll Cardiol Img. 2009;2(5):637–47.

    Article  Google Scholar 

  132. Hirano S, Kanno S, Furuyama A. Multi-walled carbon nanotubes injure the plasma membrane of macrophages. Toxicol Appl Pharmacol. 2008;232(2):244–51.

    Article  CAS  PubMed  Google Scholar 

  133. Kanno S, Furuyama A, Hirano S. A murine scavenger receptor MARCO recognizes polystyrene nanoparticles. Toxicol Sci. 2007;97(2):398–406.

    Article  CAS  PubMed  Google Scholar 

  134. Orr GA, Chrisler WB, Cassens KJ, Tan R, Tarasevich BJ, Markillie LM, Zangar RC, Thrall BD. Cellular recognition and trafficking of amorphous silica nanoparticles by macrophage scavenger receptor A. Nanotoxicology. 2011;5(3):296–311.

    Article  CAS  PubMed  Google Scholar 

  135. Hamilton R, Buckingham S, Holian A. The effect of size on Ag nanosphere toxicity in macrophage cell models and lung epithelial cell lines is dependent on particle dissolution. Int J Mol Sci. 2014;15(4):6815–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Hsu CS, Hsu SJ, Liu WL, Chen DS, Kao JH. Association of SCARB1 Gene polymorphisms with virological response in chronic hepatitis C patients receiving pegylated interferon plus ribavirin therapy. Sci Rep. 2016;6:32303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. SR-BI and Antiviral Treatment Response in HCV [Internet]. Available from: https://clinicaltrials.gov/show/NCT02714712. Accessed on 14th Jun 2019.

  138. Genetic and Metabolism of Post-prandial HDL Particles (HDL-PP) [Internet]. Available from: https://clinicaltrials.gov/show/NCT03109067. Accessed on 14th Jun 2019.

  139. Mechanisms of Chronic Kidney Disease (CKD)-Induced Foam Cell Formation [Internet]. Available from: https://clinicaltrials.gov/show/NCT01671605. Accessed on 14th Jun 2019.

  140. A Study of Immunological Biomarkers as Predictors of Cardiovascular Events (BIOKID) [Internet]. Available from: https://clinicaltrials.gov/show/NCT02894060. Accessed on 14th Jun 2019.

  141. Zheng Y, Liu Y, Jin H, Pan S, Qian Y, Huang C, Zeng Y, Luo Q, Zeng M, Zhang Z. Scavenger receptor B1 is a potential biomarker of human nasopharyngeal carcinoma and its growth is inhibited by HDL-mimetic nanoparticles. Theranostics. 2013;3(7):477–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Amit S. Lokhande and Priyanka Jahagirdar have contributed equally.

Authors and Affiliations

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

    Amit S. Lokhande & Priyanka Jahagirdar

  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

Authors
  1. Amit S. Lokhande
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Priyanka Jahagirdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prajakta Dandekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Padma V. Devarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Padma V. Devarajan .

Editor information

Editors and Affiliations

  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

Rights and permissions

Reprints and permissions

Copyright information

© 2019 American Association of Pharmaceutical Scientists

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lokhande, A.S., Jahagirdar, P., Dandekar, P., Devarajan, P.V. (2019). Scavenger 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_10

Download citation

Publish with us

Policies and ethics

Search

Navigation