1932

Abstract

Red blood cell (RBC) hitchhiking is a method of drug delivery that can increase drug concentration in target organs by orders of magnitude. In RBC hitchhiking, drug-loaded nanoparticles (NPs) are adsorbed onto red blood cells and then injected intravascularly, which causes the NPs to transfer to cells of the capillaries in the downstream organ. RBC hitchhiking has been demonstrated in multiple species and multiple organs. For example, RBC-hitchhiking NPs localized at unprecedented levels in the brain when using intra-arterial catheters, such as those in place immediately after mechanical thrombectomy for acute ischemic stroke. RBC hitchhiking has been successfully employed in numerous preclinical models of disease, ranging from pulmonary embolism to cancer metastasis. In addition to summarizing the versatility of RBC hitchhiking, we also describe studies into the surprisingly complex mechanisms of RBC hitchhiking as well as outline future studies to further improve RBC hitchhiking's clinical utility.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-bioeng-121219-024239
2021-07-13
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/bioeng/23/1/annurev-bioeng-121219-024239.html?itemId=/content/journals/10.1146/annurev-bioeng-121219-024239&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Mulder WJM, van Leent MMT, Lameijer M, Fisher EA, Fayad ZA, Pérez-Medina C. 2018. High-density lipoprotein nanobiologics for precision medicine. Acc. Chem. Res. 51:1127–37
    [Google Scholar]
  2. 2. 
    Pack DW, Hoffman AS, Pun S, Stayton PS. 2005. Design and development of polymers for gene delivery. Nat. Rev. Drug Discov. 4:7581–93
    [Google Scholar]
  3. 3. 
    Fenton OS, Olafson KN, Pillai PS, Mitchell MJ, Langer R. 2018. Advances in biomaterials for drug delivery. Adv. Mater. 30:291705328
    [Google Scholar]
  4. 4. 
    Torchilin VP. 2014. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nat. Rev. Drug Discov. 13:11813–27
    [Google Scholar]
  5. 5. 
    Mitragotri S, Anderson DG, Chen X, Chow EK, Ho D et al. 2015. Accelerating the translation of nanomaterials in biomedicine. ACS Nano 9:76644–54
    [Google Scholar]
  6. 6. 
    Mulder WJM, Ochando J, Joosten LAB, Fayad ZA, Netea MG. 2019. Therapeutic targeting of trained immunity. Nat. Rev. Drug Discov. 18:7553–66
    [Google Scholar]
  7. 7. 
    Fu A, Tang R, Hardie J, Farkas ME, Rotello VM. 2014. Promises and pitfalls of intracellular delivery of proteins. Bioconjug. Chem. 25:91602–8
    [Google Scholar]
  8. 8. 
    Luther DC, Huang R, Jeon T, Zhang X, Lee Y-W et al. 2020. Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles. Adv. Drug Deliv. Rev. 156:188–213
    [Google Scholar]
  9. 9. 
    Pelaz B, Alexiou C, Alvarez-Puebla RA, Alves F, Andrews AM et al. 2017. Diverse applications of nanomedicine. ACS Nano 11:32313–81
    [Google Scholar]
  10. 10. 
    Muro S. 2012. Challenges in design and characterization of ligand-targeted drug delivery systems. J. Control. Release 164:2125–37
    [Google Scholar]
  11. 11. 
    Filipczak N, Pan J, Yalamarty SSK, Torchilin VP. 2020. Recent advancements in liposome technology. Adv. Drug Deliv. Rev. 156:4–22
    [Google Scholar]
  12. 12. 
    Howard MD, Hood ED, Zern B, Shuvaev VV, Grosser T, Muzykantov VR. 2014. Nanocarriers for vascular delivery of anti-inflammatory agents. Annu. Rev. Pharmacol. Toxicol. 54:205–26
    [Google Scholar]
  13. 13. 
    Yang R, Wei T, Goldberg H, Wang W, Cullion K, Kohane DS. 2017. Getting drugs across biological barriers. Adv. Mater. 29:371606596
    [Google Scholar]
  14. 14. 
    Jiang Y, Huo S, Hardie J, Liang X-J, Rotello VM. 2016. Progress and perspective of inorganic nanoparticle-based siRNA delivery systems. Expert Opin. Drug Deliv. 13:4547–59
    [Google Scholar]
  15. 15. 
    Oltra NS, Nair P, Discher DE. 2014. From stealthy polymersomes and filomicelles to “self” peptide-nanoparticles for cancer therapy. Annu. Rev. Chem. Biomol. Eng. 5:281–99
    [Google Scholar]
  16. 16. 
    Discher DE, Eisenberg A. 2002. Polymer vesicles. Science 297:5583967–73
    [Google Scholar]
  17. 17. 
    Hunter AC, Elsom J, Wibroe PP, Moghimi SM. 2012. Polymeric particulate technologies for oral drug delivery and targeting: a pathophysiological perspective. Nanomedicine 8:Suppl. 1S5–20
    [Google Scholar]
  18. 18. 
    Timko BP, Dvir T, Kohane DS. 2010. Remotely triggerable drug delivery systems. Adv. Mater. 22:444925–43
    [Google Scholar]
  19. 19. 
    Pillai JD, Dunn SS, Napier ME, DeSimone JM. 2011. Novel platforms for vascular carriers with controlled geometry. IUBMB Life 63:8596–606
    [Google Scholar]
  20. 20. 
    Getts R, Muro S. 2016. DNA-based drug carriers: the paradox of a classical “cargo” material becoming a versatile “carrier” to overcome barriers in drug delivery. Curr. Pharm. Des. 22:91245–58
    [Google Scholar]
  21. 21. 
    Yoo J-W, Irvine DJ, Discher DE, Mitragotri S. 2011. Bio-inspired, bioengineered and biomimetic drug delivery carriers. Nat. Rev. Drug Discov. 10:7521–35
    [Google Scholar]
  22. 22. 
    Parhiz H, Khoshnejad M, Myerson JW, Hood E, Patel PN et al. 2018. Unintended effects of drug carriers: big issues of small particles. Adv. Drug Deliv. Rev. 130:90–112
    [Google Scholar]
  23. 23. 
    Moghimi SM, Simberg D, Papini E, Farhangrazi ZS. 2020. Complement activation by drug carriers and particulate pharmaceuticals: principles, challenges and opportunities. Adv. Drug Deliv. Rev. 157:83–95
    [Google Scholar]
  24. 24. 
    Jeong KJ, Kohane DS. 2011. Surface modification and drug delivery for biointegration. Ther. Deliv. 2:6737–52
    [Google Scholar]
  25. 25. 
    Moghimi SM. 2018. Nanomedicine safety in preclinical and clinical development: focus on idiosyncratic injection/infusion reactions. Drug Discov. Today 23:51034–42
    [Google Scholar]
  26. 26. 
    Moghimi SM, Simberg D, Skotland T, Yaghmur A, Hunter AC. 2019. The interplay between blood proteins, complement, and macrophages on nanomedicine performance and responses. J. Pharmacol. Exp. Ther. 370:3581–92
    [Google Scholar]
  27. 27. 
    Boraschi D, Italiani P, Palomba R, Decuzzi P, Duschl A et al. 2017. Nanoparticles and innate immunity: new perspectives on host defence. Semin. Immunol. 34:33–51
    [Google Scholar]
  28. 28. 
    Brenner JS, Bhamidipati K, Glassman P, Ramakrishnan N, Jiang D et al. 2017. Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions. Nanomedicine 13:41495–506
    [Google Scholar]
  29. 29. 
    Myerson JW, Anselmo AC, Liu Y, Mitragotri S, Eckmann DM, Muzykantov VR. 2016. Non-affinity factors modulating vascular targeting of nano- and microcarriers. Adv. Drug Deliv. Rev. 99:Part A97–112
    [Google Scholar]
  30. 30. 
    Howard M, Zern BJ, Anselmo AC, Shuvaev VV, Mitragotri S, Muzykantov V. 2014. Vascular targeting of nanocarriers: perplexing aspects of the seemingly straightforward paradigm. ACS Nano 8:54100–32
    [Google Scholar]
  31. 31. 
    Villa CH, Pan DC, Zaitsev S, Cines DB, Siegel DL, Muzykantov VR. 2015. Delivery of drugs bound to erythrocytes: new avenues for an old intravascular carrier. Ther. Deliv. 6:7795–826
    [Google Scholar]
  32. 32. 
    Ihler GM. 1982. Erythrocytes as carriers for glucocerebrosidase. Prog. Clin. Biol. Res. 95:655–67
    [Google Scholar]
  33. 33. 
    Muzykantov VR, Sakharov DV, Smirnov MD, Domogatsky SP, Samokhin GP. 1985. Targeting of enzyme immobilized on erythrocyte membrane to collagen-coated surface. FEBS Lett 182:162–66
    [Google Scholar]
  34. 34. 
    Rossi L, Serafini S, Pierigé F, Antonelli A, Cerasi A et al. 2005. Erythrocyte-based drug delivery. Expert Opin. Drug Deliv. 2:2311–22
    [Google Scholar]
  35. 35. 
    Magnani M, Bianchi M, Rossi L, Stocchi V. 1989. Human red blood cells as bioreactors for the release of 2′,3′-dideoxycytidine, an inhibitor of HIV infectivity. Biochem. Biophys. Res. Commun. 164:1446–52
    [Google Scholar]
  36. 36. 
    Bailleul C, Kravtzoff R, Chestier N, Laguerre M, Chassaigne M, Ropars C. 1990. Several aspects of red blood cell engineering: potential therapeutic applications. Biomed. Biochim. Acta 49:2–3S344–49
    [Google Scholar]
  37. 37. 
    Mambrini G, Mandolini M, Rossi L, Pierigè F, Capogrossi G et al. 2017. Ex vivo encapsulation of dexamethasone sodium phosphate into human autologous erythrocytes using fully automated biomedical equipment. Int. J. Pharm. 517:1–2175–84
    [Google Scholar]
  38. 38. 
    Antonelli A, Sfara C, Weber O, Pison U, Manuali E et al. 2016. Characterization of ferucarbotran-loaded RBCs as long circulating magnetic contrast agents. Nanomedicine 11:212781–95
    [Google Scholar]
  39. 39. 
    Castro M, Rossi L, Papadatou B, Bracci F, Knafelz D et al. 2007. Long-term treatment with autologous red blood cells loaded with dexamethasone 21-phosphate in pediatric patients affected by steroid-dependent Crohn disease. J. Pediatr. Gastroenterol. Nutr. 44:4423–26
    [Google Scholar]
  40. 40. 
    Villa CH, Cines DB, Siegel DL, Muzykantov V. 2017. Erythrocytes as carriers for drug delivery in blood transfusion and beyond. Transfus. Med. Rev. 31:126–35
    [Google Scholar]
  41. 41. 
    Rossi L, Pierigè F, Aliano MP, Magnani M. 2020. Ongoing developments and clinical progress in drug-loaded red blood cell technologies. BioDrugs 34:3265–72
    [Google Scholar]
  42. 42. 
    Bossa F, Latiano A, Rossi L, Magnani M, Palmieri O et al. 2008. Erythrocyte-mediated delivery of dexamethasone in patients with mild-to-moderate ulcerative colitis, refractory to mesalamine: a randomized, controlled study. Am. J. Gastroenterol. 103:102509–16
    [Google Scholar]
  43. 43. 
    Rossi L, Serafini S, Pierigé F, Castro M, Ambrosini MI et al. 2006. Erythrocytes as a controlled drug delivery system: clinical evidences. J. Control. Release 116:2e43–45
    [Google Scholar]
  44. 44. 
    Al-Abd AM, Aljehani ZK, Gazzaz RW, Fakhri SH, Jabbad AH et al. 2015. Pharmacokinetic strategies to improve drug penetration and entrapment within solid tumors. J. Control. Release 219:269–77
    [Google Scholar]
  45. 45. 
    Ropars C, Avenard G, Chassaigne M. 1987. Large-scale entrapment of drugs into resealed red blood cells using a continuous-flow dialysis system. Methods Enzymol 149:242–48
    [Google Scholar]
  46. 46. 
    Dale GL. 1987. High-efficiency entrapment of enzymes in resealed red cell ghosts by dialysis. Methods Enzymol 149:229–34
    [Google Scholar]
  47. 47. 
    Rossi L, Pierigè F, Antonelli A, Bigini N, Gabucci C et al. 2016. Engineering erythrocytes for the modulation of drugs’ and contrasting agents' pharmacokinetics and biodistribution. Adv. Drug Deliv. Rev. 106:Part A73–87
    [Google Scholar]
  48. 48. 
    Fraternale A, Rossi L, Magnani M. 1996. Encapsulation, metabolism and release of 2-fluoro-ara-AMP from human erythrocytes. Biochim. Biophys. Acta 1291:2149–54
    [Google Scholar]
  49. 49. 
    Bourgeaux V, Lanao JM, Bax BE, Godfrin Y. 2016. Drug-loaded erythrocytes: on the road toward marketing approval. Drug Des. Devel. Ther. 10:665–76
    [Google Scholar]
  50. 50. 
    Flower R, Peiretti E, Magnani M, Rossi L, Serafini S et al. 2008. Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells. Investig. Ophthalmol. Vis. Sci. 49:125510–16
    [Google Scholar]
  51. 51. 
    Kontos S, Hubbell JA. 2010. Improving protein pharmacokinetics by engineering erythrocyte affinity. Mol. Pharm. 7:62141–47
    [Google Scholar]
  52. 52. 
    Rossi L, Pierigè F, Carducci C, Gabucci C, Pascucci T et al. 2014. Erythrocyte-mediated delivery of phenylalanine ammonia lyase for the treatment of phenylketonuria in BTBR-Pahenu2 mice. J. Control. Release 194:37–44
    [Google Scholar]
  53. 53. 
    Magnani M, Rossi L. 2014. Approaches to erythrocyte-mediated drug delivery. Expert Opin. Drug Deliv. 11:5677–87
    [Google Scholar]
  54. 54. 
    Antonelli A, Pacifico S, Sfara C, Tamma M, Magnani M 2018. Ferucarbotran-loaded red blood cells as long circulating MRI contrast agents: first in vivo results in mice. Nanomedicine 13:7675–87
    [Google Scholar]
  55. 55. 
    Markov DE, Boeve H, Gleich B, Borgert J, Antonelli A et al. 2010. Human erythrocytes as nanoparticle carriers for magnetic particle imaging. Phys. Med. Biol. 55:216461–73
    [Google Scholar]
  56. 56. 
    Ganguly K, Krasik T, Medinilla S, Bdeir K, Cines DB et al. 2005. Blood clearance and activity of erythrocyte-coupled fibrinolytics. J. Pharmacol. Exp. Ther. 312:31106–13
    [Google Scholar]
  57. 57. 
    Muzykantov VR, Sakharov DV, Smirnov MD, Samokhin GP, Smirnov VN. 1986. Immunotargeting of erythrocyte-bound streptokinase provides local lysis of a fibrin clot. Biochim. Biophys. Acta 884:2355–62
    [Google Scholar]
  58. 58. 
    Magnani M, Chiarantini L, Mancini U. 1994. Preparation and characterization of biotinylated red blood cells. Biotechnol. Appl. Biochem. 20:3335–45
    [Google Scholar]
  59. 59. 
    Huang N-J, Pishesha N, Mukherjee J, Zhang S, Deshycka R et al. 2017. Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin. Nat. Commun. 8:1423
    [Google Scholar]
  60. 60. 
    Pishesha N, Bilate AM, Wibowo MC, Huang N-J, Li Z et al. 2017. Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease. PNAS 114:123157–62
    [Google Scholar]
  61. 61. 
    Zaitsev S, Spitzer D, Murciano J-C, Ding B-S, Tliba S et al. 2010. Targeting of a mutant plasminogen activator to circulating red blood cells for prophylactic fibrinolysis. J. Pharmacol. Exp. Ther. 332:31022–31
    [Google Scholar]
  62. 62. 
    Muzykantov VR. 2010. Drug delivery by red blood cells: vascular carriers designed by mother nature. Expert Opin. Drug Deliv. 7:4403–27
    [Google Scholar]
  63. 63. 
    Zaitsev S, Danielyan K, Murciano J-C, Ganguly K, Krasik T et al. 2006. Human complement receptor type 1–directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis. Blood 108:61895–902
    [Google Scholar]
  64. 64. 
    Villa CH, Pan DC, Johnston IH, Greineder CF, Walsh LR et al. 2018. Biocompatible coupling of therapeutic fusion proteins to human erythrocytes. Blood Adv 2:3165–76
    [Google Scholar]
  65. 65. 
    Zaitsev S, Kowalska MA, Neyman M, Carnemolla R, Tliba S et al. 2012. Targeting recombinant thrombomodulin fusion protein to red blood cells provides multifaceted thromboprophylaxis. Blood 119:204779–85
    [Google Scholar]
  66. 66. 
    Armstead WM, Ganguly K, Riley J, Zaitsev S, Cines DB et al. 2012. RBC-coupled tPA prevents whereas tPA aggravates JNK MAPK-mediated impairment of ATP- and Ca-sensitive K channel-mediated cerebrovasodilation after cerebral photothrombosis. Transl. Stroke Res. 3:1114–21
    [Google Scholar]
  67. 67. 
    Armstead WM, Ganguly K, Kiessling JW, Chen X-H, Smith DH et al. 2009. Red blood cells-coupled tPA prevents impairment of cerebral vasodilatory responses and tissue injury in pediatric cerebral hypoxia/ischemia through inhibition of ERK MAPK activation. J. Cereb. Blood Flow Metab. 29:81463–74
    [Google Scholar]
  68. 68. 
    Spitzer D, Unsinger J, Mao D, Wu X, Molina H, Atkinson JP. 2005. In vivo correction of complement regulatory protein deficiency with an inhibitor targeting the red blood cell membrane. J. Immunol. 175:117763–70
    [Google Scholar]
  69. 69. 
    Spitzer D, Unsinger J, Bessler M, Atkinson JP. 2004. ScFv-mediated in vivo targeting of DAF to erythrocytes inhibits lysis by complement. Mol. Immunol. 40:13911–19
    [Google Scholar]
  70. 70. 
    Murciano J-C, Medinilla S, Eslin D, Atochina E, Cines DB, Muzykantov VR. 2003. Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes. Nat. Biotechnol. 21:8891–96
    [Google Scholar]
  71. 71. 
    Carnemolla R, Villa CH, Greineder CF, Zaitsev S, Patel KR et al. 2017. Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia-reperfusion injury. FASEB J 31:2761–70
    [Google Scholar]
  72. 72. 
    Gersh KC, Zaitsev S, Cines DB, Muzykantov V, Weisel JW. 2011. Flow-dependent channel formation in clots by an erythrocyte-bound fibrinolytic agent. Blood 117:184964–67
    [Google Scholar]
  73. 73. 
    Murciano J-C, Higazi AA-R, Cines DB, Muzykantov VR. 2009. Soluble urokinase receptor conjugated to carrier red blood cells binds latent pro-urokinase and alters its functional profile. J. Control. Release 139:3190–96
    [Google Scholar]
  74. 74. 
    Ganguly K, Murciano J-C, Westrick R, Leferovich J, Cines DB, Muzykantov VR. 2007. The glycocalyx protects erythrocyte-bound tissue-type plasminogen activator from enzymatic inhibition. J. Pharmacol. Exp. Ther. 321:1158–64
    [Google Scholar]
  75. 75. 
    Zaitsev S, Spitzer D, Murciano J-C, Ding B-S, Tliba S et al. 2010. Sustained thromboprophylaxis mediated by an RBC-targeted pro-urokinase zymogen activated at the site of clot formation. Blood 115:255241–48
    [Google Scholar]
  76. 76. 
    Danielyan K, Ganguly K, Ding B-S, Atochin D, Zaitsev S et al. 2008. Cerebrovascular thromboprophylaxis in mice by erythrocyte-coupled tissue-type plasminogen activator. Circulation 118:141442–49
    [Google Scholar]
  77. 77. 
    Philips GR, Gleich B, Paredes-Juarez GA, Antonelli A, Magnani M, Bulte JWM. 2019. Magnetic manipulation of blood conductivity with superparamagnetic iron oxide-loaded erythrocytes. ACS Appl. Mater. Interfaces 11:1211194–201
    [Google Scholar]
  78. 78. 
    Antonelli A, Szwargulski P, Scarpa E-S, Thieben F, Cordula G et al. 2020. Development of long circulating magnetic particle imaging tracers: use of novel magnetic nanoparticles and entrapment into human erythrocytes. Nanomedicine 15:8739–53
    [Google Scholar]
  79. 79. 
    Villa CH, Anselmo AC, Mitragotri S, Muzykantov V. 2016. Red blood cells: supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems. Adv. Drug Deliv. Rev. 106:Part A88–103
    [Google Scholar]
  80. 80. 
    Peeters PA, Claessens CA, Eling WM, Crommelin DJ. 1988. Immunospecific targeting of liposomes to erythrocytes. Biochem. Pharmacol. 37:112215–22
    [Google Scholar]
  81. 81. 
    Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R. 1994. Biodegradable long-circulating polymeric nanospheres. Science 263:51531600–3
    [Google Scholar]
  82. 82. 
    Mozar FS, Chowdhury EH. 2018. Impact of PEGylated nanoparticles on tumor targeted drug delivery. Curr. Pharm. Des. 24:283283–96
    [Google Scholar]
  83. 83. 
    Hoang Thi TT, Pilkington EH, Nguyen DH, Lee JS, Park KD, Truong NP. 2020. The importance of poly(ethylene glycol) alternatives for overcoming PEG immunogenicity in drug delivery and bioconjugation. Polymers 12:2298
    [Google Scholar]
  84. 84. 
    Chambers E, Mitragotri S. 2004. Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. J. Control. Release 100:1111–19
    [Google Scholar]
  85. 85. 
    Chambers E, Mitragotri S. 2007. Long circulating nanoparticles via adhesion on red blood cells: mechanism and extended circulation. Exp. Biol. Med. 232:7958–66
    [Google Scholar]
  86. 86. 
    Anselmo AC, Gupta V, Zern BJ, Pan D, Zakrewsky M et al. 2013. Delivering nanoparticles to lungs while avoiding liver and spleen through adsorption on red blood cells. ACS Nano 7:1211129–37
    [Google Scholar]
  87. 87. 
    Marcos-Contreras OA, Brenner JS, Kiseleva RY, Zuluaga-Ramirez V, Greineder CF et al. 2019. Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted versus untargeted nanocarriers in the inflamed brain. J. Control. Release 301:54–61
    [Google Scholar]
  88. 88. 
    Brenner JS, Pan DC, Myerson JW, Marcos-Contreras OA, Villa CH et al. 2018. Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude. Nat. Commun. 9:12684
    [Google Scholar]
  89. 89. 
    Kuebler WM, Goetz AE. 2002. The marginated pool. Eur. Surg. Res. 34:1–292–100
    [Google Scholar]
  90. 90. 
    Zelepukin IV, Yaremenko AV, Shipunova VO, Babenyshev AV, Balalaeva IV et al. 2019. Nanoparticle-based drug delivery via RBC-hitchhiking for the inhibition of lung metastases growth. Nanoscale 11:41636–46
    [Google Scholar]
  91. 91. 
    Zhao Z, Ukidve A, Gao Y, Kim J, Mitragotri S. 2019. Erythrocyte leveraged chemotherapy (ELeCt): nanoparticle assembly on erythrocyte surface to combat lung metastasis. Sci. Adv. 5:11eaax9250
    [Google Scholar]
  92. 92. 
    Hess C, Schifferli JA. 2003. Immune adherence revisited: novel players in an old game. Physiology 18:3104–8
    [Google Scholar]
  93. 93. 
    Nelson RA Jr. 1953. The immune-adherence phenomenon; an immunologically specific reaction between microorganisms and erythrocytes leading to enhanced phagocytosis. Science 118:3077733–37
    [Google Scholar]
  94. 94. 
    Domínguez M, Toraño A. 2001. Leishmania immune adherence reaction in vertebrates. Parasite Immunol 23:5259–65
    [Google Scholar]
  95. 95. 
    Lachgar A, Jaureguiberry G, Le Buenac H, Bizzini B, Zagury JF et al. 1998. Binding of HIV-1 to RBCs involves the Duffy Antigen Receptors for Chemokines (DARC). Biomed. Pharmacother. 52:10436–39
    [Google Scholar]
  96. 96. 
    Hess C, Klimkait T, Schlapbach L, Del Zenero V, Sadallah S et al. 2002. Association of a pool of HIV-1 with erythrocytes in vivo: a cohort study. Lancet 359:93252230–34
    [Google Scholar]
  97. 97. 
    Paccaud JP, Carpentier JL, Schifferli JA. 1988. Direct evidence for the clustered nature of complement receptors type 1 on the erythrocyte membrane. J. Immunol. 141:113889–94
    [Google Scholar]
  98. 98. 
    Schifferli JA, Ng YC, Paccaud JP, Walport MJ. 1989. The role of hypocomplementaemia and low erythrocyte complement receptor type 1 numbers in determining abnormal immune complex clearance in humans. Clin. Exp. Immunol. 75:3329–35
    [Google Scholar]
  99. 99. 
    Taylor RP, Reist CJ, Sutherland WM, Otto A, Labuguen RH, Wright EL. 1992. In vivo binding and clearance of circulating antigen by bispecific heteropolymer-mediated binding to primate erythrocyte complement receptor. J. Immunol. 148:82462–68
    [Google Scholar]
  100. 100. 
    Taylor RP, Sutherland WM, Reist CJ, Webb DJ, Wright EL, Labuguen RH 1991. Use of heteropolymeric monoclonal antibodies to attach antigens to the C3b receptor of human erythrocytes: a potential therapeutic treatment. PNAS 88:83305–9
    [Google Scholar]
  101. 101. 
    Magnani M, Balestra E, Fraternale A, Aquaro S, Paiardini M et al. 2003. Drug-loaded red blood cell-mediated clearance of HIV-1 macrophage reservoir by selective inhibition of STAT1 expression. J. Leukoc. Biol. 74:5764–71
    [Google Scholar]
  102. 102. 
    Chiarantini L, Argnani R, Zucchini S, Stevanato L, Zabardi P et al. 1997. Red blood cells as delivery system for recombinant HSV-1 glycoprotein B: immunogenicity and protection in mice. Vaccine 15:3276–80
    [Google Scholar]
  103. 103. 
    Sabatino R, Antonelli A, Battistelli S, Schwendener R, Magnani M, Rossi L. 2014. Macrophage depletion by free bisphosphonates and zoledronate-loaded red blood cells. PLOS ONE 9:6e101260
    [Google Scholar]
  104. 104. 
    Biagiotti S, Rossi L, Bianchi M, Giacomini E, Pierigè F et al. 2011. Immunophilin-loaded erythrocytes as a new delivery strategy for immunosuppressive drugs. J. Control. Release 154:3306–13
    [Google Scholar]
  105. 105. 
    Boberg A, Dominici S, Brave A, Hallermalm K, Hinkula J et al. 2007. Immunization with HIV protease peptides linked to syngeneic erythrocytes. Infect. Agents Cancer 2:9
    [Google Scholar]
  106. 106. 
    Magnani M, Chiarantini L, Vittoria E, Mancini U, Rossi L, Fazi A. 1992. Red blood cells as an antigen-delivery system. Biotechnol. Appl. Biochem. 16:2188–94
    [Google Scholar]
  107. 107. 
    Grimm AJ, Kontos S, Diaceri G, Quaglia-Thermes X, Hubbell JA. 2015. Memory of tolerance and induction of regulatory T cells by erythrocyte-targeted antigens. Sci. Rep. 5:15907
    [Google Scholar]
  108. 108. 
    Lorentz KM, Kontos S, Diaceri G, Henry H, Hubbell JA. 2015. Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase. Sci. Adv. 1:6e1500112
    [Google Scholar]
  109. 109. 
    Dominici S, Laguardia ME, Serafini G, Chiarantini L, Fortini C et al. 2003. Red blood cell-mediated delivery of recombinant HIV-1 Tat protein in mice induces anti-Tat neutralizing antibodies and CTL. Vaccine 21:17–182073–81
    [Google Scholar]
  110. 110. 
    Kontos S, Kourtis IC, Dane KY, Hubbell JA 2013. Engineering antigens for in situ erythrocyte binding induces T-cell deletion. PNAS 110:1E60–68
    [Google Scholar]
  111. 111. 
    Ji W, Smith PN, Koepsel RR, Andersen JD, Baker SL et al. 2020. Erythrocytes as carriers of immunoglobulin-based therapeutics. Acta Biomater 101:422–35
    [Google Scholar]
  112. 112. 
    Ukidve A, Zhao Z, Fehnel A, Krishnan V, Pan DC et al. 2020. Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function. PNAS 117:3017727–36
    [Google Scholar]
  113. 113. 
    Irvine DJ, Aung A, Silva M. 2020. Controlling timing and location in vaccines. Adv. Drug Deliv. Rev. 158:91–115
    [Google Scholar]
  114. 114. 
    Gary EN, Weiner DB. 2020. DNA vaccines: Prime time is now. Curr. Opin. Immunol. 65:21–27
    [Google Scholar]
  115. 115. 
    Pardi N, Hogan MJ, Weissman D. 2020. Recent advances in mRNA vaccine technology. Curr. Opin. Immunol. 65:14–20
    [Google Scholar]
  116. 116. 
    Weiss C, Carriere M, Fusco L, Capua I, Regla-Nava JA et al. 2020. Toward nanotechnology-enabled approaches against the COVID-19 pandemic. ACS Nano 14:66383–406
    [Google Scholar]
  117. 117. 
    Irvine DJ, Read BJ. 2020. Shaping humoral immunity to vaccines through antigen-displaying nanoparticles. Curr. Opin. Immunol. 65:1–6
    [Google Scholar]
  118. 118. 
    Greineder CF, Johnston IH, Villa CH, Gollomp K, Esmon CT et al. 2017. ICAM-1-targeted thrombomodulin mitigates tissue factor-driven inflammatory thrombosis in a human endothelialized microfluidic model. Blood Adv 1:181452–65
    [Google Scholar]
  119. 119. 
    Greineder CF, Chacko A-M, Zaytsev S, Zern BJ, Carnemolla R et al. 2013. Vascular immunotargeting to endothelial determinant ICAM-1 enables optimal partnering of recombinant scFv-thrombomodulin fusion with endogenous cofactor. PLOS ONE 8:11e80110
    [Google Scholar]
  120. 120. 
    Kolhar P, Anselmo AC, Gupta V, Pant K, Prabhakarpandian B et al. 2013. Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium. PNAS 110:2610753–58
    [Google Scholar]
  121. 121. 
    Champion JA, Katare YK, Mitragotri S. 2007. Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers. J. Control. Release 121:1–23–9
    [Google Scholar]
  122. 122. 
    Anselmo AC, Kumar S, Gupta V, Pearce AM, Ragusa A et al. 2015. Exploiting shape, cellular-hitchhiking and antibodies to target nanoparticles to lung endothelium: synergy between physical, chemical and biological approaches. Biomaterials 68:1–8
    [Google Scholar]
  123. 123. 
    Muzykantov VR. 2013. Drug delivery carriers on the fringes: natural red blood cells versus synthetic multilayered capsules. Expert Opin. Drug Deliv. 10:11–4
    [Google Scholar]
  124. 124. 
    Villa CH, Seghatchian J, Muzykantov V. 2016. Drug delivery by erythrocytes: “Primum non nocere. .” Transfus. Apher. Sci. 55:3275–80
    [Google Scholar]
  125. 125. 
    Corsi D, Paiardini M, Crinelli R, Bucchini A, Magnani M. 1999. Alteration of α-spectrin ubiquitination due to age-dependent changes in the erythrocyte membrane. Eur. J. Biochem. 261:3775–83
    [Google Scholar]
  126. 126. 
    Magnani M, Papa S, Rossi L, Vitale M, Fornaini G, Manzoli FA. 1988. Membrane-bound immunoglobulins increase during red blood cell aging. Acta Haematol 79:3127–32
    [Google Scholar]
  127. 127. 
    Oldenborg PA, Zheleznyak A, Fang YF, Lagenaur CF, Gresham HD, Lindberg FP. 2000. Role of CD47 as a marker of self on red blood cells. Science 288:54732051–54
    [Google Scholar]
  128. 128. 
    Zaltzman AB, Van den Berg CW, Muzykantov VR, Morgan BP. 1995. Enhanced complement susceptibility of avidin-biotin-treated human erythrocytes is a consequence of neutralization of the complement regulators CD59 and decay accelerating factor. Biochem. J. 307:Part 3651–56
    [Google Scholar]
  129. 129. 
    Muzykantov VR, Smirnov MD, Klibanov AL. 1993. Avidin attachment to biotinylated amino groups of the erythrocyte membrane eliminates homologous restriction of both classical and alternative pathways of the complement. FEBS Lett 318:2108–12
    [Google Scholar]
  130. 130. 
    Muzykantov VR, Smirnov MD, Samokhin GP. 1992. Avidin-induced lysis of biotinylated erythrocytes by homologous complement via the alternative pathway depends on avidin's ability of multipoint binding with biotinylated membrane. Biochim. Biophys. Acta 1107:1119–25
    [Google Scholar]
  131. 131. 
    Muzykantov VR, Taylor RP. 1994. Attachment of biotinylated antibody to red blood cells: antigen-binding capacity of immunoerythrocytes and their susceptibility to lysis by complement. Anal. Biochem. 223:1142–48
    [Google Scholar]
  132. 132. 
    Muzykantov VR, Smirnov MD, Zaltzman AB, Samokhin GP. 1993. Tannin-mediated attachment of avidin provides complement-resistant immunoerythrocytes that can be lysed in the presence of activator of complement. Anal. Biochem. 208:2338–42
    [Google Scholar]
  133. 133. 
    Muzykantov VR, Smirnov MD, Klibanov AL. 1993. Avidin attachment to red blood cells via a phospholipid derivative of biotin provides complement-resistant immunoerythrocytes. J. Immunol. Methods 158:2183–90
    [Google Scholar]
  134. 134. 
    Chiarantini L, Rossi L, Fraternale A, Magnani M. 1995. Modulated red blood cell survival by membrane protein clustering. Mol. Cell. Biochem. 144:153–59
    [Google Scholar]
  135. 135. 
    Suzuki T, Dale GL 1988. Senescent erythrocytes: isolation of in vivo aged cells and their biochemical characteristics. PNAS 85:51647–51
    [Google Scholar]
  136. 136. 
    Pan D, Vargas-Morales O, Zern B, Anselmo AC, Gupta V et al. 2016. The effect of polymeric nanoparticles on biocompatibility of carrier red blood cells. PLOS ONE 11:3e0152074
    [Google Scholar]
  137. 137. 
    Muzykantov VR, Murciano JC, Taylor RP, Atochina EN, Herraez A. 1996. Regulation of the complement-mediated elimination of red blood cells modified with biotin and streptavidin. Anal. Biochem. 241:1109–19
    [Google Scholar]
  138. 138. 
    Pan DC, Myerson JW, Brenner JS, Patel PN, Anselmo AC et al. 2018. Nanoparticle properties modulate their attachment and effect on carrier red blood cells. Sci. Rep. 8:11615
    [Google Scholar]
  139. 139. 
    Muzykantov VR, Smirnov MD, Samokhin GP. 1991. Avidin attachment to biotinylated erythrocytes induces homologous lysis via the alternative pathway of complement. Blood 78:102611–18
    [Google Scholar]
/content/journals/10.1146/annurev-bioeng-121219-024239
Loading
/content/journals/10.1146/annurev-bioeng-121219-024239
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error