1932

Abstract

Accompanying the increasing translational impact of immunotherapeutic strategies to treat and prevent disease has been a broadening interest across both bioscience and bioengineering in the lymphatic system. Herein, the lymphatic system physiology, ranging from its tissue structures to immune functions and effects, is described. Design principles and engineering approaches to analyze and manipulate this tissue system in nanoparticle-based drug delivery applications are also elaborated.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-bioeng-092222-034906
2023-06-08
2024-12-03
Loading full text...

Full text loading...

/deliver/fulltext/bioeng/25/1/annurev-bioeng-092222-034906.html?itemId=/content/journals/10.1146/annurev-bioeng-092222-034906&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Swartz M. 2001. The physiology of the lymphatic system. Adv. Drug Deliv. Rev. 50:3–20. https://doi.org/10.1016/S0169-409X(01)00150-8
    [Crossref] [Google Scholar]
  2. 2.
    Sherwood L. 2013. Human Physiology: From Cells to Systems Belmont, CA: Brooks/Cole, Cengage Learning. , 8th ed..
    [Google Scholar]
  3. 3.
    Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E et al. 2007. Functionally specialized junctions between endothelial cells of lymphatic vessels. J. Exp. Med. 204:2349–62. https://doi.org/10.1084/jem.20062596
    [Crossref] [Google Scholar]
  4. 4.
    Mäkinen T, Adams RH, Bailey J, Lu Q, Ziemiecki A et al. 2005. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev. 19:397–410. https://doi.org/10.1101/gad.330105
    [Crossref] [Google Scholar]
  5. 5.
    Zhang F, Zarkada G, Yi S, Eichmann A 2020. Lymphatic endothelial cell junctions: molecular regulation in physiology and diseases. Front. Physiol. 11:509 https://doi.org/10.3389/fphys.2020.00509
    [Google Scholar]
  6. 6.
    Schudel A, Francis DM, Thomas SN. 2019. Material design for lymph node drug delivery. Nat. Rev. Mater. 4:415–28. https://doi.org/10.1038/s41578-019-0110-7
    [Google Scholar]
  7. 7.
    Yao L-C, Baluk P, Srinivasan RS, Oliver G, McDonald DM. 2012. Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation. Am. J. Pathol. 180:2561–75. https://doi.org/10.1016/j.ajpath.2012.02.019
    [Google Scholar]
  8. 8.
    Gerli R, Solito R, Weber E, Agliano M. 2000. Specific adhesion molecules bind anchoring filaments and endothelial cells in human skin initial lymphatics. Lymphology 33:148–57
    [Google Scholar]
  9. 9.
    Pflicke H, Sixt M. 2009. Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels. J. Exp. Med. 206:2925–35. https://doi.org/10.1084/jem.20091739
    [Google Scholar]
  10. 10.
    Triacca V, Güç E, Kilarski WW, Pisano M, Swartz MA. 2017. Transcellular pathways in lymphatic endothelial cells regulate changes in solute transport by fluid stress. Circ. Res. 120:1440–52. https://doi.org/10.1161/CIRCRESAHA.116.309828
    [Crossref] [Google Scholar]
  11. 11.
    McCright J, Skeen C, Yarmovsky J, Maisel K. 2022. Nanoparticles with dense poly(ethylene glycol) coatings with near neutral charge are maximally transported across lymphatics and to the lymph nodes. Acta Biomater. 145:146–58. https://doi.org/10.1016/j.actbio.2022.03.054
    [Google Scholar]
  12. 12.
    Zawieja DC, Davis KL, Schuster R, Hinds WM, Granger HJ. 1993. Distribution, propagation, and coordination of contractile activity in lymphatics. Am. J. Physiol. Heart Circ. Physiol. 264:H1283–91. https://doi.org/10.1152/ajpheart.1993.264.4.H1283
    [Crossref] [Google Scholar]
  13. 13.
    Zawieja DC. 2009. Contractile physiology of lymphatics. Lymphat. Res. Biol. 7:87–96. https://doi.org/10.1089/lrb.2009.0007
    [Crossref] [Google Scholar]
  14. 14.
    Tso P, Balint JA. 1986. Formation and transport of chylomicrons by enterocytes to the lymphatics. Am. J. Physiol. 250:G715–26. https://doi.org/10.1152/ajpgi.1986.250.6.G715
    [Google Scholar]
  15. 15.
    Xiao C, Stahel P, Lewis GF. 2019. Regulation of chylomicron secretion: focus on post-assembly mechanisms. Cell. Mol. Gastroenterol. Hepatol. 7:487–501. https://doi.org/10.1016/j.jcmgh.2018.10.015
    [Google Scholar]
  16. 16.
    Dixon JB. 2010. Mechanisms of chylomicron uptake into lacteals. Ann. N. Y. Acad. Sci. 1207:E52–57. https://doi.org/10.1111/j.1749-6632.2010.05716.x
    [Google Scholar]
  17. 17.
    Elz AS, Trevaskis NL, Porter CJH, Bowen JM, Prestidge CA. 2022. Smart design approaches for orally administered lipophilic prodrugs to promote lymphatic transport. J. Control. Release 341:676–701. https://doi.org/10.1016/j.jconrel.2021.12.003
    [Google Scholar]
  18. 18.
    Bernier-Latmani J, Petrova T. 2017. Intestinal lymphatic vasculature: structure, mechanisms and functions. Nat. Rev. Gastroenterol. Hepatol. 14:510–26. https://doi.org/10.1038/nrgastro.2017.79
    [Google Scholar]
  19. 19.
    Hokkanen K, Tirronen A, Ylä-Herttuala S. 2019. Intestinal lymphatic vessels and their role in chylomicron absorption and lipid homeostasis. Curr. Opin. Lipidol. 30:5370–76. https://doi.org/10.1097/MOL.0000000000000626
    [Crossref] [Google Scholar]
  20. 20.
    Petrova TV, Koh GY. 2020. Biological functions of lymphatic vessels. Science 369:6500eaax4063 https://doi.org/10.1126/science.aax4063
    [Google Scholar]
  21. 21.
    O'Melia MJ, Lund AW, Thomas SN. 2019. The biophysics of lymphatic transport: engineering tools and immunological consequences. iScience 22:28–43. https://doi.org/10.1016/j.isci.2019.11.005
    [Google Scholar]
  22. 22.
    Oliver G, Kipnis J, Randolph GJ, Harvey NL. 2020. The lymphatic vasculature in the 21st century: novel functional roles in homeostasis and disease. Cell 182:2270–96. https://doi.org/10.1016/j.cell.2020.06.039
    [Crossref] [Google Scholar]
  23. 23.
    Churchill MJ, du Bois H, Heim TA, Mudianto T, Steele MM et al. 2022. Infection-induced lymphatic zippering restricts fluid transport and viral dissemination from skin. J. Exp. Med. 219:5e20211830 https://doi.org/10.1084/jem.20211830
    [Google Scholar]
  24. 24.
    Kataru RP, Baik JE, Park HJ, Wiser I, Rehal S et al. 2019. Regulation of immune function by the lymphatic system in lymphedema. Front. Immunol. 10:470 https://doi.org/10.3389/fimmu.2019.00470
    [Google Scholar]
  25. 25.
    Roozendaal R, Mempel TR, Pitcher LA, Gonzalez SF, Verschoor A et al. 2009. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30:264–76. https://doi.org/10.1016/j.immuni.2008.12.014
    [Crossref] [Google Scholar]
  26. 26.
    Zhang Y-N, Lazarovits J, Poon W, Ouyang B, Nguyen LNM et al. 2019. Nanoparticle size influences antigen retention and presentation in lymph node follicles for humoral immunity. Nano Lett. 19:7226–35. https://doi.org/10.1021/acs.nanolett.9b02834
    [Google Scholar]
  27. 27.
    Asano K, Nabeyama A, Miyake Y, Qiu CH, Kurita A et al. 2011. CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 34:85–95. https://doi.org/10.1016/j.immuni.2010.12.011
    [Crossref] [Google Scholar]
  28. 28.
    Reynoso GV, Weisberg AS, Shannon JP, McManus DT, Shores L et al. 2019. Lymph node conduits transport virions for rapid T cell activation. Nat. Immunol. 20:602–12. https://doi.org/10.1038/s41590-019-0342-0
    [Crossref] [Google Scholar]
  29. 29.
    Pape KA, Catron DM, Itano AA, Jenkins MK. 2007. The humoral immune response is initiated in lymph nodes by B cells that acquire soluble antigen directly in the follicles. Immunity 26:491–502. https://doi.org/10.1016/j.immuni.2007.02.011
    [Google Scholar]
  30. 30.
    Rantakari P, Auvinen K, Jäppinen N, Kapraali M, Valtonen J et al. 2015. The endothelial protein PLVAP in lymphatics controls the entry of lymphocytes and antigens into lymph nodes. Nat. Immunol. 16:386–96. https://doi.org/10.1038/ni.3101
    [Google Scholar]
  31. 31.
    Gretz JE, Norbury CC, Anderson AO, Proudfoot AEI, Shaw S. 2000. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J. Exp. Med. 192:1425–40. https://doi.org/10.1084/jem.192.10.1425
    [Google Scholar]
  32. 32.
    Sixt M, Kanazawa N, Selg M, Samson T, Roos G et al. 2005. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 22:19–29. https://doi.org/10.1016/j.immuni.2004.11.013
    [Google Scholar]
  33. 33.
    Dzieciatkowska M, Wohlauer MV, Moore EE, Damle S, Peltz E et al. 2011. Proteomic analysis of human mesenteric lymph. Shock 35:331–38. https://doi.org/10.1097/SHK.0b013e318206f654
    [Google Scholar]
  34. 34.
    Dzieciatkowska M, D'Alessandro A, Moore EE, Wohlauer M, Banerjee A et al. 2014. Lymph is not a plasma ultrafiltrate: a proteomic analysis of injured patients. Shock 42:485–98. https://doi.org/10.1097/SHK.0000000000000249
    [Crossref] [Google Scholar]
  35. 35.
    Clement CC, Santambrogio L. 2013. The lymph self-antigen repertoire. Front. Immunol. 4:424
    [Google Scholar]
  36. 36.
    Clement CC, Cannizzo ES, Nastke M-D, Sahu R, Olszewski W et al. 2010. An expanded self-antigen peptidome is carried by the human lymph as compared to the plasma. PLOS ONE 5:e9863 https://doi.org/10.1371/journal.pone.0009863
    [Crossref] [Google Scholar]
  37. 37.
    Clement CC, Rotzschke O, Santambrogio L. 2011. The lymph as a pool of self-antigens. Trends Immunol. 32:6–11. https://doi.org/10.1016/j.it.2010.10.004
    [Google Scholar]
  38. 38.
    Clement CC, Aphkhazava D, Nieves E, Callaway M, Olszewski W et al. 2013. Protein expression profiles of human lymph and plasma mapped by 2D-DIGE and 1D SDS–PAGE coupled with nanoLC–ESI–MS/MS bottom-up proteomics. J. Proteom. 78:172–87. https://doi.org/10.1016/j.jprot.2012.11.013
    [Google Scholar]
  39. 39.
    Clement CC, Becerra A, Yin L, Zolla V, Huang L et al. 2016. The dendritic cell major histocompatibility complex II (MHC II) peptidome derives from a variety of processing pathways and includes peptides with a broad spectrum of HLA-DM sensitivity. J. Biol. Chem. 291:5576–95. https://doi.org/10.1074/jbc.M115.655738
    [Crossref] [Google Scholar]
  40. 40.
    D'Alessandro A, Dzieciatkowska M, Peltz ED, Moore EE, Jordan JR et al. 2014. Dynamic changes in rat mesenteric lymph proteins following trauma using label-free mass spectrometry. Shock 42:509–17. https://doi.org/10.1097/SHK.0000000000000259
    [Crossref] [Google Scholar]
  41. 41.
    Fang J-F, Shih L-Y, Yuan K-C, Fang K-Y, Hwang T-L, Hsieh S-Y. 2010. Proteomic analysis of post-hemorrhagic shock mesenteric lymph. Shock 34:291–98
    [Google Scholar]
  42. 42.
    Goldfinch GM, Smith WD, Imrie L, McLean K, Inglis NF, Pemberton AD. 2008. The proteome of gastric lymph in normal and nematode infected sheep. Proteomics 8:1909–18. https://doi.org/10.1002/pmic.200700531
    [Crossref] [Google Scholar]
  43. 43.
    Meng Z, Veenstra TD. 2007. Proteomic analysis of serum, plasma, and lymph for the identification of biomarkers. Prot. Clin. Appl. 1:747–57. https://doi.org/10.1002/prca.200700243
    [Google Scholar]
  44. 44.
    Nguyen VPKH, Hanna G, Rodrigues N, Pizzuto K, Yang E et al. 2010. Differential proteomic analysis of lymphatic, venous, and arterial endothelial cells extracted from bovine mesenteric vessels. Proteomics 10:1658–72. https://doi.org/10.1002/pmic.200900594
    [Google Scholar]
  45. 45.
    Zurawel A, Moore EE, Peltz ED, Jordan JR, Damle S et al. 2010. Proteomic profiling of the mesenteric lymph after hemorrhagic shock: differential gel electrophoresis and mass spectrometry analysis. Clin. Proteom. 8:1 https://doi.org/10.1186/1559-0275-8-1
    [Google Scholar]
  46. 46.
    Zhang P, Li Y, Zhang L-D, Wang L-H, Wang X et al. 2014. Proteome changes in mesenteric lymph induced by sepsis. Mol. Med. Rep. 10:2793–804. https://doi.org/10.3892/mmr.2014.2580
    [Google Scholar]
  47. 47.
    Diebel LN, Liberati DM, Ledgerwood AM, Lucas CE. 2012. Changes in lymph proteome induced by hemorrhagic shock: the appearance of damage-associated molecular patterns. J. Trauma Acute Care Surg. 73:41–51. https://doi.org/10.1097/TA.0b013e31825e8b32
    [Google Scholar]
  48. 48.
    Mittal A, Middleditch M, Ruggiero K, Buchanan CM, Jullig M et al. 2008. The proteome of rodent mesenteric lymph. Am. J. Physiol. Gastrointest. Liver Physiol. 295:G895–903. https://doi.org/10.1152/ajpgi.90378.2008
    [Crossref] [Google Scholar]
  49. 49.
    Broggi MAS, Maillat L, Clement CC, Bordry N, Corthésy P et al. 2019. Tumor-associated factors are enriched in lymphatic exudate compared to plasma in metastatic melanoma patients. J. Exp. Med. 216:1091–107. https://doi.org/10.1084/jem.20181618
    [Google Scholar]
  50. 50.
    Ekström K, Crescitelli R, Pétursson HI, Johansson J, Lässer C et al. 2022. Characterization of surface markers on extracellular vesicles isolated from lymphatic exudate from patients with breast cancer. BMC Cancer 22:50 https://doi.org/10.1186/s12885-021-08870-w
    [Google Scholar]
  51. 51.
    Tessandier N, Melki I, Cloutier N, Allaeys I, Miszta A et al. 2020. Platelets disseminate extracellular vesicles in lymph in rheumatoid arthritis. ATVB 40:929–42. https://doi.org/10.1161/ATVBAHA.119.313698
    [Crossref] [Google Scholar]
  52. 52.
    Milasan A, Tessandier N, Tan S, Brisson A, Boilard E, Martel C. 2016. Extracellular vesicles are present in mouse lymph and their level differs in atherosclerosis. J. Extracell. Vesicles 5:31427 https://doi.org/10.3402/jev.v5.31427
    [Crossref] [Google Scholar]
  53. 53.
    García-Silva S, Benito-Martín A, Nogués L, Hernández-Barranco A, Mazariegos MS et al. 2021. Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nat. Cancer 2:1387–405. https://doi.org/10.1038/s43018-021-00272-y
    [Google Scholar]
  54. 54.
    Leary N, Walser S, He Y, Cousin N, Pereira P et al. 2022. Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. J. Extracell. Vesicles 11:e12197 https://doi.org/10.1002/jev2.12197
    [Google Scholar]
  55. 55.
    Hampton HR, Chtanova T. 2019. Lymphatic migration of immune cells. Front. Immunol. 10:1168 https://doi.org/10.3389/fimmu.2019.01168
    [Google Scholar]
  56. 56.
    Arasa J, Collado-Diaz V, Halin C. 2021. Structure and immune function of afferent lymphatics and their mechanistic contribution to dendritic cell and T cell trafficking. Cells 10:1269 https://doi.org/10.3390/cells10051269
    [Crossref] [Google Scholar]
  57. 57.
    Loo CP, Nelson NA, Lane RS, Booth JL, Loprinzi Hardin SC et al. 2017. Lymphatic vessels balance viral dissemination and immune activation following cutaneous viral infection. Cell Rep. 20:3176–87. https://doi.org/10.1016/j.celrep.2017.09.006
    [Crossref] [Google Scholar]
  58. 58.
    Thomas SN, Rutkowski JM, Pasquier M, Kuan EL, Alitalo K et al. 2012. Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage. J. Immunol. 189:2181–90. https://doi.org/10.4049/jimmunol.1103545
    [Google Scholar]
  59. 59.
    Churchill MJ, du Bois H, Heim TA, Mudianto T, Steele MM et al. 2022. Infection-induced lymphatic zippering restricts fluid transport and viral dissemination from skin. J. Exp. Med. 219:e20211830 https://doi.org/10.1084/jem.20211830
    [Google Scholar]
  60. 60.
    Suh SH, Choe K, Hong SP, Jeong S, Makinen T et al. 2019. Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages. EMBO Rep. 20:e46927 https://doi.org/10.15252/embr.201846927
    [Crossref] [Google Scholar]
  61. 61.
    Zhang F, Zarkada G, Han J, Li J, Dubrac A et al. 2018. Lacteal junction zippering protects against diet-induced obesity. 361599–603
  62. 62.
    O'Melia MJ, Rohner NA, Manspeaker MP, Francis DM, Kissick HT, Thomas SN. 2020. Quality of CD8+ T cell immunity evoked in lymph nodes is compartmentalized by route of antigen transport and functional in tumor context. Sci. Adv. 6:eabd7134 https://doi.org/10.1126/sciadv.abd7134
    [Google Scholar]
  63. 63.
    Czepielewski RS, Erlich EC, Onufer EJ, Young S, Saunders BT et al. 2021. Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor. Immunity 54:2795–811.e9. https://doi.org/10.1016/j.immuni.2021.10.003
    [Google Scholar]
  64. 64.
    Czepielewski R, Erlich E, Onufer E, Young S, Kim K-W et al. 2021. Obstructed lymphatic transport and leakage driven by mesenteric tertiary lymphoid organs is a feature of Crohn's disease mouse model. Gastroenterology 160:S45 https://doi.org/10.1053/j.gastro.2021.01.125
    [Google Scholar]
  65. 65.
    Maisel K, Hrusch CL, Medellin JEG, Potin L, Chapel DB et al. 2021. Pro-lymphangiogenic VEGFR-3 signaling modulates memory T cell responses in allergic airway inflammation. Mucosal Immunol. 14:144–51. https://doi.org/10.1038/s41385-020-0308-4
    [Google Scholar]
  66. 66.
    Wang X-L, Zhao J, Qin L, Cao J-L. 2016. VEGFR-3 blocking deteriorates inflammation with impaired lymphatic function and different changes in lymphatic vessels in acute and chronic colitis. Am. J. Transl. Res. 8:827–41
    [Google Scholar]
  67. 67.
    Nihei M, Okazaki T, Ebihara S, Kobayashi M, Niu K et al. 2015. Chronic inflammation, lymphangiogenesis, and effect of an anti-VEGFR therapy in a mouse model and in human patients with aspiration pneumonia. J. Pathol. 235:632–45. https://doi.org/10.1002/path.4473
    [Google Scholar]
  68. 68.
    Sato H, Higashiyama M, Hozumi H, Sato S, Furuhashi H et al. 2016. Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis. Am. J. Physiol. Gastrointest. Liver Physiol. 311:G276–85. https://doi.org/10.1152/ajpgi.00455.2015
    [Google Scholar]
  69. 69.
    Jurisic G, Sundberg JP, Detmar M. 2013. Blockade of VEGF receptor-3 aggravates inflammatory bowel disease and lymphatic vessel enlargement. Inflamm. Bowel Dis. 19:1983–89. https://doi.org/10.1097/MIB.0b013e31829292f7
    [Crossref] [Google Scholar]
  70. 70.
    Guo R, Zhou Q, Proulx ST, Wood R, Ji R-C et al. 2009. Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis. Arthritis Rheum. 60:2666–76. https://doi.org/10.1002/art.24764
    [Crossref] [Google Scholar]
  71. 71.
    D'Alessio S, Correale C, Tacconi C, Gandelli A, Pietrogrande G et al. 2014. VEGF-C-dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease. J. Clin. Investig. 124:3863–78. https://doi.org/10.1172/JCI72189
    [Google Scholar]
  72. 72.
    Huggenberger R, Ullmann S, Proulx ST, Pytowski B, Alitalo K, Detmar M. 2010. Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation. J. Exp. Med. 207:2255–69. https://doi.org/10.1084/jem.20100559
    [Crossref] [Google Scholar]
  73. 73.
    Schwager S, Detmar M. 2019. Inflammation and lymphatic function. Front. Immunol. 10:308 https://doi.org/10.3389/fimmu.2019.00308
    [Crossref] [Google Scholar]
  74. 74.
    Zhang L, Ocansey DKW, Liu L, Olovo CV, Zhang X et al. 2021. Implications of lymphatic alterations in the pathogenesis and treatment of inflammatory bowel disease. Biomed. Pharmacother. 140:111752 https://doi.org/10.1016/j.biopha.2021.111752
    [Crossref] [Google Scholar]
  75. 75.
    Ryan GM, Kaminskas LM, Porter CJH. 2014. Nano-chemotherapeutics: Maximizing lymphatic drug exposure to improve the treatment of lymph-metastatic cancers. J. Control. Release 193:241–56. https://doi.org/10.1016/j.jconrel.2014.04.051
    [Crossref] [Google Scholar]
  76. 76.
    Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF. 2008. Nanoparticles target distinct dendritic cell populations according to their size. Eur. J. Immunol. 38:1404–13. https://doi.org/10.1002/eji.200737984
    [Crossref] [Google Scholar]
  77. 77.
    McCright J, Naiknavare R, Yarmovsky J, Maisel K. 2022. Targeting lymphatics for nanoparticle drug delivery. Front. Pharmacol. 13:887402 https://doi.org/10.3389/fphar.2022.887402
    [Google Scholar]
  78. 78.
    Sestito LF, To K, Cribb M, Archer PA, Thomas SN, Dixon JB. 2023. Lymphatic-draining nanoparticles deliver Bay K8644 payload to lymphatic vessels and enhance their pumping function. Sci. Adv. 9:eabq0435 https://doi.org/10.1126/sciadv.abq0435
    [Google Scholar]
  79. 79.
    Desai J, Thakkar H. 2022. Mechanistic evaluation of lymphatic targeting efficiency of atazanavir sulfate loaded lipid nanocarriers: in-vitro and in-vivo studies. J. Drug Deliv. Sci. Technol. 68:103090 https://doi.org/10.1016/j.jddst.2021.103090
    [Crossref] [Google Scholar]
  80. 80.
    Obinu A, Burrai GP, Cavalli R, Galleri G, Migheli R et al. 2021. Transmucosal solid lipid nanoparticles to improve genistein absorption via intestinal lymphatic transport. Pharmaceutics 13:267 https://doi.org/10.3390/pharmaceutics13020267
    [Crossref] [Google Scholar]
  81. 81.
    Kim KS, Kwag DS, Hwang HS, Lee ES, Bae YH. 2018. Immense insulin intestinal uptake and lymphatic transport using bile acid conjugated partially uncapped liposome. Mol. Pharm. 15:4756–63. https://doi.org/10.1021/acs.molpharmaceut.8b00708
    [Crossref] [Google Scholar]
  82. 82.
    Kim KS, Suzuki K, Cho H, Youn YS, Bae YH. 2018. Oral nanoparticles exhibit specific high-efficiency intestinal uptake and lymphatic transport. ACS Nano 12:8893–900. https://doi.org/10.1021/acsnano.8b04315
    [Crossref] [Google Scholar]
  83. 83.
    Kim KS, Suzuki K, Cho H, Bae YH. 2020. Selected factors affecting oral bioavailability of nanoparticles surface-conjugated with glycocholic acid via intestinal lymphatic pathway. Mol. Pharm. 17:4346–53. https://doi.org/10.1021/acs.molpharmaceut.0c00764
    [Crossref] [Google Scholar]
  84. 84.
    Kim KS, Youn YS, Bae YH. 2019. Immune-triggered cancer treatment by intestinal lymphatic delivery of docetaxel-loaded nanoparticle. J. Control. Release 311–12:85–95. https://doi.org/10.1016/j.jconrel.2019.08.027
    [Crossref] [Google Scholar]
  85. 85.
    Baek J-S, Cho C-W. 2017. Surface modification of solid lipid nanoparticles for oral delivery of curcumin: improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake. Eur. J. Pharm. Biopharm. 117:132–40. https://doi.org/10.1016/j.ejpb.2017.04.013
    [Google Scholar]
  86. 86.
    Landh E, Moir LM, Traini D, Young PM, Ong HX. 2020. Properties of rapamycin solid lipid nanoparticles for lymphatic access through the lungs & part II: the effect of nanoparticle charge. Nanomedicine 15:1947–63. https://doi.org/10.2217/nnm-2020-0192
    [Google Scholar]
  87. 87.
    Landh E, Moir LM, Bradbury P, Traini D, Young PM, Ong HX. 2020. Properties of rapamycin solid lipid nanoparticles for lymphatic access through the lungs & part I: the effect of size. Nanomedicine 15:1927–45. https://doi.org/10.2217/nnm-2020-0077
    [Google Scholar]
  88. 88.
    Zhao P, Le Z, Liu L, Chen Y. 2020. Therapeutic delivery to the brain via the lymphatic vasculature. Nano Lett. 20:5415–20. https://doi.org/10.1021/acs.nanolett.0c01806
    [Google Scholar]
  89. 89.
    Miao Y, Lin Y, Chen K, Luo P, Chuang S et al. 2021. Engineering nano- and microparticles as oral delivery vehicles to promote intestinal lymphatic drug transport. Adv. Mater. 33:2104139 https://doi.org/10.1002/adma.202104139
    [Crossref] [Google Scholar]
  90. 90.
    Bisso S, Degrassi A, Brambilla D, Leroux J-C. 2019. Poly(ethylene glycol)-alendronate coated nanoparticles for magnetic resonance imaging of lymph nodes. J. Drug Target. 27:659–69. https://doi.org/10.1080/1061186X.2018.1545235
    [Crossref] [Google Scholar]
  91. 91.
    Kuroda C, Ajima K, Ueda K, Sobajima A, Yoshida K et al. 2021. Isolated lymphatic vessel lumen perfusion system for assessing nanomaterial movements and nanomaterial-induced responses in lymphatic vessels. Nano Today 36:101018 https://doi.org/10.1016/j.nantod.2020.101018
    [Google Scholar]
  92. 92.
    Howard GP, Verma G, Ke X, Thayer WM, Hamerly T et al. 2019. Critical size limit of biodegradable nanoparticles for enhanced lymph node trafficking and paracortex penetration. Nano Res. 12:837–44. https://doi.org/10.1007/s12274-019-2301-3
    [Crossref] [Google Scholar]
  93. 93.
    Rohner NA, Thomas SN. 2017. Flexible macromolecule versus rigid particle retention in the injected skin and accumulation in draining lymph nodes are differentially influenced by hydrodynamic size. ACS Biomater. Sci. Eng. 3:153–59. https://doi.org/10.1021/acsbiomaterials.6b00438
    [Google Scholar]
  94. 94.
    Schudel A, Kassis T, Dixon JB, Thomas SN. 2015. S-nitrosated polypropylene sulfide nanoparticles for thiol-dependent transnitrosation and toxicity against adult female filarial worms. Adv. Healthcare Mater. 4:1484–90. https://doi.org/10.1002/adhm.201400841
    [Google Scholar]
  95. 95.
    Schudel A, Chapman AP, Yau M-K, Higginson CJ, Francis DM et al. 2020. Programmable multistage drug delivery to lymph nodes. Nat. Nanotechnol. 15:491–99. https://doi.org/10.1038/s41565-020-0679-4
    [Google Scholar]
  96. 96.
    Archer PA, Sestito LF, Manspeaker MP, O'Melia MJ, Rohner NA et al. 2021. Quantitation of lymphatic transport mechanism and barrier influences on lymph node-resident leukocyte access to lymph-borne macromolecules and drug delivery systems. Drug Deliv. Transl. Res. 11:2328–43. https://doi.org/10.1007/s13346-021-01015-3
    [Crossref] [Google Scholar]
  97. 97.
    O'Neill NA, Eppler HB, Jewell CM, Bromberg JS. 2018. Harnessing the lymph node microenvironment. Curr. Opin. Organ Transplant. 23:173–82. https://doi.org/10.1097/MOT.0000000000000488
    [Google Scholar]
  98. 98.
    Qian Y, Jin H, Qiao S, Dai Y, Huang C et al. 2016. Targeting dendritic cells in lymph node with an antigen peptide-based nanovaccine for cancer immunotherapy. Biomaterials 98:171–83. https://doi.org/10.1016/j.biomaterials.2016.05.008
    [Crossref] [Google Scholar]
  99. 99.
    Platt CD, Ma JK, Chalouni C, Ebersold M, Bou-Reslan H et al. 2010. Mature dendritic cells use endocytic receptors to capture and present antigens. PNAS 107:4287–92. https://doi.org/10.1073/pnas.0910609107
    [Crossref] [Google Scholar]
  100. 100.
    Inaba K, Turley S, Iyoda T, Yamaide F, Shimoyama S et al. 2000. The formation of immunogenic major histocompatibility complex class II–peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J. Exp. Med. 191:927–36. https://doi.org/10.1084/jem.191.6.927
    [Google Scholar]
  101. 101.
    Zhang Z, Chen J, Ding L, Jin H, Lovell JF et al. 2010. HDL-mimicking peptide–lipid nanoparticles with improved tumor targeting. Small 6:430–37. https://doi.org/10.1002/smll.200901515
    [Google Scholar]
  102. 102.
    Zhang Z, Cao W, Jin H, Lovell JF, Yang M et al. 2009. Biomimetic nanocarrier for direct cytosolic drug delivery. Angew. Chem. Int. Ed. 48:9171–75. https://doi.org/10.1002/anie.200903112
    [Google Scholar]
  103. 103.
    Cruz LJ, Rosalia RA, Kleinovink JW, Rueda F, Löwik CWGM, Ossendorp F. 2014. Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8+ T cell response: a comparative study. J. Control. Release 192:209–18. https://doi.org/10.1016/j.jconrel.2014.07.040
    [Google Scholar]
  104. 104.
    Azzi J, Yin Q, Uehara M, Ohori S, Tang L et al. 2016. Targeted delivery of immunomodulators to lymph nodes. Cell Rep. 15:1202–13. https://doi.org/10.1016/j.celrep.2016.04.007
    [Google Scholar]
  105. 105.
    Francis DM, Manspeaker MP, Archer PA, Sestito LF, Heiler AJ et al. 2021. Drug-eluting immune checkpoint blockade antibody-nanoparticle conjugate enhances locoregional and systemic combination cancer immunotherapy through T lymphocyte targeting. Biomaterials 279:121184 https://doi.org/10.1016/j.biomaterials.2021.121184
    [Crossref] [Google Scholar]
  106. 106.
    Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S-I et al. 2004. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. 199:815–24. https://doi.org/10.1084/jem.20032220
    [Google Scholar]
  107. 107.
    Ishihara A, Ishihara J, Watkins EA, Tremain AC, Nguyen M et al. 2021. Prolonged residence of an albumin–IL-4 fusion protein in secondary lymphoid organs ameliorates experimental autoimmune encephalomyelitis. Nat. Biomed. Eng. 5:387–98. https://doi.org/10.1038/s41551-020-00627-3
    [Google Scholar]
  108. 108.
    Yang X, Lian K, Meng T, Liu X, Miao J et al. 2018. Immune adjuvant targeting micelles allow efficient dendritic cell migration to lymph nodes for enhanced cellular immunity. ACS Appl. Mater. Interfaces 10:33532–44. https://doi.org/10.1021/acsami.8b10081
    [Google Scholar]
  109. 109.
    Schmid D, Park CG, Hartl CA, Subedi N, Cartwright AN et al. 2017. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nat. Commun. 8:1747 https://doi.org/10.1038/s41467-017-01830-8
    [Crossref] [Google Scholar]
  110. 110.
    Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. 2016. Extracellular matrix structure. Adv. Drug Deliv. Rev. 97:4–27. https://doi.org/10.1016/j.addr.2015.11.001
    [Google Scholar]
  111. 111.
    Nance EA, Woodworth GF, Sailor KA, Shih T-Y, Xu Q et al. 2012. A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci. Transl. Med. 4:149ra119 https://doi.org/10.1126/scitranslmed.3003594
    [Google Scholar]
  112. 112.
    Ramirez A, Merwitz B, Lee H, Vaughan E, Maisel K. 2022. Multiple particle tracking (MPT) using PEGylated nanoparticles reveals heterogeneity within murine lymph nodes and between lymph nodes at different locations. Biomater. Sci. 10:6992–7003
    [Google Scholar]
  113. 113.
    Castanos-Velez E, Biberfeld P, Patarroyo M. 1995. Extracellular matrix proteins and integrin receptors in reactive and non-reactive lymph nodes. 86270–78
  114. 114.
    Horsnell HL, Tetley RJ, De Belly H, Makris S, Millward LJ et al. 2022. Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics. Nat. Immunol. 23:1169–82. https://doi.org/10.1038/s41590-022-01272-5
    [Crossref] [Google Scholar]
  115. 115.
    Martinez VG, Pankova V, Krasny L, Singh T, Makris S et al. 2019. Fibroblastic reticular cells control conduit matrix deposition during lymph node expansion. Cell Rep. 29:2810–22.e5. https://doi.org/10.1016/j.celrep.2019.10.103
    [Crossref] [Google Scholar]
  116. 116.
    Dadras SS, Paul T, Bertoncini J, Brown LF, Muzikansky A et al. 2003. Tumor lymphangiogenesis. Am. J. Pathol. 162:1951–60. https://doi.org/10.1016/S0002-9440(10)64328-3
    [Google Scholar]
  117. 117.
    Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG et al. 2005. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J. Clin. Investig. 115:247–57. https://doi.org/10.1172/JCI22037
    [Crossref] [Google Scholar]
  118. 118.
    Gregory JL, Walter A, Alexandre YO, Hor JL, Liu R et al. 2017. Infection programs sustained lymphoid stromal cell responses and shapes lymph node remodeling upon secondary challenge. Cell Rep. 18:406–18. https://doi.org/10.1016/j.celrep.2016.12.038
    [Google Scholar]
  119. 119.
    Huang L, Deng J, Xu W, Wang H, Shi L et al. 2018. CD8+ T cells with high TGFβ1 expression cause lymph node fibrosis following HIV infection. Mol. Med. Rep. 18:77–86. https://doi.org/10.3892/mmr.2018.8964
    [Crossref] [Google Scholar]
  120. 120.
    Güç E, Briquez PS, Foretay D, Fankhauser MA, Hubbell JA et al. 2017. Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C promotes wound healing by increasing immune cell trafficking and matrix remodeling. Biomaterials 131:160–75. https://doi.org/10.1016/j.biomaterials.2017.03.033
    [Crossref] [Google Scholar]
  121. 121.
    Rohner NA, McClain J, Tuell SL, Warner A, Smith B et al. 2015. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage. FASEB J. 29:4512–22. https://doi.org/10.1096/fj.15-274761
    [Crossref] [Google Scholar]
  122. 122.
    Hood JL, San RS, Wickline SA. 2011. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 71:3792–801. https://doi.org/10.1158/0008-5472.CAN-10-4455
    [Google Scholar]
  123. 123.
    Mu W, Rana S, Zöller M 2013. Host matrix modulation by tumor exosomes promotes motility and invasiveness. Neoplasia 15:875–87. https://doi.org/10.1593/neo.13786
    [Google Scholar]
  124. 124.
    Nathanson SD, Mahan M. 2011. Sentinel lymph node pressure in breast cancer. Ann. Surg. Oncol. 18:3791–96. https://doi.org/10.1245/s10434-011-1796-y
    [Google Scholar]
  125. 125.
    Riedel A, Shorthouse D, Haas L, Hall BA, Shields J. 2016. Tumor-induced stromal reprogramming drives lymph node transformation. Nat. Immunol. 17:1118–27. https://doi.org/10.1038/ni.3492
    [Google Scholar]
  126. 126.
    Pucci F, Garris C, Lai CP, Newton A, Pfirschke C et al. 2016. SCS macrophages suppress melanoma by restricting tumor-derived vesicle–B cell interactions. Science 352:242–46. https://doi.org/10.1126/science.aaf1328
    [Crossref] [Google Scholar]
  127. 127.
    Kim J, Francis DM, Sestito LF, Archer PA, Manspeaker MP et al. 2022. Thermosensitive hydrogel releasing nitric oxide donor and anti-CTLA-4 micelles for anti-tumor immunotherapy. Nat. Commun. 13:1479 https://doi.org/10.1038/s41467-022-29121-x
    [Google Scholar]
  128. 128.
    Yang B, Cai B, Deng P, Wu X, Guan Y et al. 2015. Nitric oxide increases arterial endotheial permeability through mediating VE-cadherin expression during arteriogenesis. PLOS ONE 10:e0127931 https://doi.org/10.1371/journal.pone.0127931
    [Crossref] [Google Scholar]
  129. 129.
    Durán WN, Beuve AV, Sánchez FA. 2013. Nitric oxide, S-nitrosation, and endothelial permeability. IUBMB Life 65:819–26. https://doi.org/10.1002/iub.1204
    [Google Scholar]
  130. 130.
    Sestito LF, Thomas SN. 2021. Lymph-directed nitric oxide increases immune cell access to lymph-borne nanoscale solutes. Biomaterials 265:120411 https://doi.org/10.1016/j.biomaterials.2020.120411
    [Google Scholar]
  131. 131.
    Silva M, Kato Y, Melo MB, Phung I, Freeman BL et al. 2021. A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity. Sci. Immunol. 6:eabf1152 https://doi.org/10.1126/sciimmunol.abf1152
    [Crossref] [Google Scholar]
  132. 132.
    Zhang Y-N, Poon W, Sefton E, Chan WCW. 2020. Suppressing subcapsular sinus macrophages enhances transport of nanovaccines to lymph node follicles for robust humoral immunity. ACS Nano 14:9478–90. https://doi.org/10.1021/acsnano.0c02240
    [Google Scholar]
  133. 133.
    Maisel K, Sasso MS, Potin L, Swartz M. 2017. Exploiting lymphatic vessels for immunomodulation: rationale, opportunities, and challenges. Adv. Drug Del. Rev. 114:43–59
    [Google Scholar]
/content/journals/10.1146/annurev-bioeng-092222-034906
Loading
/content/journals/10.1146/annurev-bioeng-092222-034906
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