Top

Current Diabetes Reports

Published in:

01-10-2017 | Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

Authors: Tobias Neef, Stephen D. Miller

Published in: Current Diabetes Reports | Issue 10/2017

Abstract

Purpose of Review

The current standard therapy for type 1 diabetes (T1D) is insulin replacement. Autoimmune diseases are typically treated with broad immunosuppression, but this has multiple disadvantages. Induction of antigen-specific tolerance is preferable. The application of nanomedicine to the problem of T1D can take different forms, but one promising way is the development of tolerogenic nanoparticles, the aim of which is to mitigate the islet-destroying autoimmunity. We review the topic and highlight recent strategies to produce tolerogenic nanoparticles for the purpose of treating T1D.

Recent Findings

Several groups are making progress in applying tolerogenic nanoparticles to rodent models of T1D, while others are using nanotechnology to aid other potential T1D treatments such as islet transplant and islet encapsulation.

Summary

The strategies behind how nanoparticles achieve tolerance are varied. It is likely the future will see even greater diversity in tolerance induction strategies as well as a greater focus on how to translate this technology from preclinical use in mice to treatment of T1D in humans.

In’t VP. Insulitis in human type 1 diabetes: a comparison between patients and animal models. Semin Immunopathol. 2014;36(5):569–79. doi:10.1007/s00281-014-0438-4.CrossRef

Veiseh O, Tang BC, Whitehead KA, Anderson DG, Langer R. Managing diabetes with nanomedicine: challenges and opportunities. Nat Rev Drug Discov. 2015;14(1):45–57. doi:10.1038/nrd4477.PubMedCrossRef

Kyi M, Wentworth JM, Nankervis AJ, Fourlanos S, Colman PG. Recent advances in type 1 diabetes. Med J Aust. 2015;203(7):290–3.PubMedCrossRef

McCarthy DP, Hunter ZN, Chackerian B, Shea LD, Miller SD. Targeted immunomodulation using antigen-conjugated nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2014;6(3):298–315. doi:10.1002/wnan.1263.PubMedPubMedCentralCrossRef

• Getts DR, Shea LD, Miller SD, King NJ. Harnessing nanoparticles for immune modulation. Trends Immunol. 2015;36(7):419–27. doi:10.1016/j.it.2015.05.007. A comprehensive review on the use of nanoparticles for immune modulation and tolerance. PubMedPubMedCentralCrossRef

Serra P, Santamaria P. Nanoparticle-based autoimmune disease therapy. Clin Immunol. 2015;160(1):3–13. doi:10.1016/j.clim.2015.02.003.PubMedCrossRef

Hanninen A, Jalkanen S, Salmi M, Toikkanen S, Nikolakaros G, Simell O. Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus. J Clin Invest. 1992;90(5):1901–10. doi:10.1172/JCI116067.PubMedPubMedCentralCrossRef

Lernmark A, Kloppel G, Stenger D, Vathanaprida C, Falt K, Landin-Olsson M, et al. Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus. Virchows Arch. 1995;425(6):631–40.PubMedCrossRef

Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol. 2009;155(2):173–81. doi:10.1111/j.1365-2249.2008.03860.x.PubMedPubMedCentralCrossRef

10.

Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, et al. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med. 2012;209(1):51–60. doi:10.1084/jem.20111187.PubMedPubMedCentralCrossRef

11.

Eisenbarth GS. Banting lecture 2009: an unfinished journey: molecular pathogenesis to prevention of type 1A diabetes. Diabetes. 2010;59(4):759–74. doi:10.2337/db09-1855.PubMedPubMedCentralCrossRef

12.

Pihoker C, Gilliam LK, Hampe CS, Lernmark A. Autoantibodies in diabetes. Diabetes. 2005;54(Suppl 2):S52–61.PubMedCrossRef

13.

Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A. 2007;104(43):17040–5. doi:10.1073/pnas.0705894104.PubMedPubMedCentralCrossRef

14.

Wenzlau JM, Liu Y, Yu L, Moua O, Fowler KT, Rangasamy S, et al. A common nonsynonymous single nucleotide polymorphism in the SLC30A8 gene determines ZnT8 autoantibody specificity in type 1 diabetes. Diabetes. 2008;57(10):2693–7. doi:10.2337/db08-0522.PubMedPubMedCentralCrossRef

15.

Palmer JP, Asplin CM, Clemons P, Lyen K, Tatpati O, Raghu PK, et al. Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science. 1983;222(4630):1337–9.PubMedCrossRef

16.

Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, et al. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature. 1990;347(6289):151–6. doi:10.1038/347151a0.PubMedCrossRef

17.

Lampasona V, Bearzatto M, Genovese S, Bosi E, Ferrari M, Bonifacio E. Autoantibodies in insulin-dependent diabetes recognize distinct cytoplasmic domains of the protein tyrosine phosphatase-like IA-2 autoantigen. J Immunol. 1996;157(6):2707–11.PubMed

18.

Bingley PJ, Christie MR, Bonifacio E, Bonfanti R, Shattock M, Fonte MT, et al. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes. 1994;43(11):1304–10.PubMedCrossRef

19.

Skyler JS, Ricordi C. Stopping type 1 diabetes: attempts to prevent or cure type 1 diabetes in man. Diabetes. 2011;60(1):1–8. doi:10.2337/db10-1114.PubMedPubMedCentralCrossRef

20.

Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014;383(9911):69–82. doi:10.1016/S0140-6736(13)60591-7.PubMedCrossRef

21.

Vives M, Somoza N, Soldevila G, Gomis R, Lucas A, Sanmarti A, et al. Reevaluation of autoantibodies to islet cell membrane in IDDM. Failure to detect islet cell surface antibodies using human islet cells as substrate. Diabetes. 1992;41(12):1624–31.PubMedCrossRef

22.

Koczwara K, Bonifacio E, Ziegler AG. Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes. Diabetes. 2004;53(1):1–4.PubMedCrossRef

23.

Pathiraja V, Kuehlich JP, Campbell PD, Krishnamurthy B, Loudovaris T, Coates PT, et al. Proinsulin-specific, HLA-DQ8, and HLA-DQ8-transdimer-restricted CD4+ T cells infiltrate islets in type 1 diabetes. Diabetes. 2015;64(1):172–82. doi:10.2337/db14-0858.PubMedCrossRef

24.

Skowera A, Ellis RJ, Varela-Calvino R, Arif S, Huang GC, Van-Krinks C, et al. CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope. J Clin Invest. 2008;118(10):3390–402. doi:10.1172/JCI35449.PubMedPubMedCentral

25.

Panina-Bordignon P, Lang R, van Endert PM, Benazzi E, Felix AM, Pastore RM, et al. Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. J Exp Med. 1995;181(5):1923–7.PubMedCrossRef

26.

Unger WW, Pearson T, Abreu JR, Laban S, van der Slik AR, der Kracht SM, et al. Islet-specific CTL cloned from a type 1 diabetes patient cause beta-cell destruction after engraftment into HLA-A2 transgenic NOD/scid/IL2RG null mice. PLoS One. 2012;7(11):e49213. doi:10.1371/journal.pone.0049213.PubMedPubMedCentralCrossRef

27.

Mannering SI, Pathiraja V, Kay TW. The case for an autoimmune aetiology of type 1 diabetes. Clin Exp Immunol. 2016;183(1):8–15. doi:10.1111/cei.12699.PubMedCrossRef

28.

•• Babon JA, ME DN, Blodgett DM, Crevecoeur I, Buttrick TS, Maehr R, et al. Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes. Nat Med. 2016;22(12):1482–7. doi:10.1038/nm.4203. The first comprehensive description of specificity of islet-infiltrating T cells from human donors with T1D. PubMedPubMedCentralCrossRef

29.

Jayasimhan A, Mansour KP, Slattery RM. Advances in our understanding of the pathophysiology of type 1 diabetes: lessons from the NOD mouse. Clin Sci (Lond). 2014;126(1):1–18. doi:10.1042/CS20120627.CrossRef

30.

Pearson JA, Wong FS, Wen L. The importance of the non obese diabetic (NOD) mouse model in autoimmune diabetes. J Autoimmun. 2016;66:76–88. doi:10.1016/j.jaut.2015.08.019.PubMedCrossRef

31.

•• Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, et al. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature. 2005;435(7039):220–3. Genetic evidence indicating that an autoimmune response to an insulin epitope drives development of T1D in NOD mice. PubMedPubMedCentralCrossRef

32.

•• Prasad S, Kohm AP, JS MM, Luo X, Miller SD. Pathogenesis of NOD diabetes is initiated by reactivity to the insulin B chain 9-23 epitope and involves functional epitope spreading. J Autoimmun. 2012;39(4):347–53. doi:10.1016/j.jaut.2012.04.005. Tolerogenic evidence that an autoimmune response to a dominant insulin epitope drives development of T1D in NOD mice and evidence for epitope spreading as disease progresses. PubMedPubMedCentralCrossRef

33.

Babad J, Geliebter A, DiLorenzo TP. T-cell autoantigens in the non-obese diabetic mouse model of autoimmune diabetes. Immunology. 2010;131(4):459–65. doi:10.1111/j.1365-2567.2010.03362.x.PubMedPubMedCentralCrossRef

34.

• Luo X, Herold KC, Miller SD. Immunotherapy of type 1 diabetes: where are we and where should we be going? Immunity, 2010. 32(4):488–99. doi:10.1016/j.immuni.2010.04.002. A comprehensive review of immune-based clinical trials in T1D patients.

35.

Berry G, Waldner H. Accelerated type 1 diabetes induction in mice by adoptive transfer of diabetogenic CD4+ T cells. J Vis Exp. 2013;75:e50389. doi:10.3791/50389.

36.

Presa M, Chen YG, Grier AE, Leiter EH, Brehm MA, Greiner DL, et al. The presence and preferential activation of regulatory T cells diminish adoptive transfer of autoimmune diabetes by polyclonal nonobese diabetic (NOD) T cell effectors into NSG versus NOD-scid mice. J Immunol. 2015;195(7):3011–9. doi:10.4049/jimmunol.1402446.PubMedPubMedCentralCrossRef

37.

Martin-Orozco N, Chung Y, Chang SH, Wang YH, Dong C. Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells. Eur J Immunol. 2009;39(1):216–24. doi:10.1002/eji.200838475.PubMedPubMedCentralCrossRef

38.

Feuerer M, Shen Y, Littman DR, Benoist C, Mathis D. How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity. 2009;31(4):654–64. doi:10.1016/j.immuni.2009.08.023.PubMedPubMedCentralCrossRef

39.

Haskins K, Portas M, Bradley B, Wegmann D, Lafferty K. T-lymphocyte clone specific for pancreatic islet antigen. Diabetes. 1988;37(10):1444–8.PubMedCrossRef

40.

Katz JD, Wang B, Haskins K, Benoist C, Mathis D. Following a diabetogenic T cell from genesis through pathogenesis. Cell. 1993;74(6):1089–100.PubMedCrossRef

41.

Stadinski BD, Delong T, Reisdorph N, Reisdorph R, Powell RL, Armstrong M, et al. Chromogranin A is an autoantigen in type 1 diabetes. Nat Immunol. 2010;11(3):225–31. doi:10.1038/ni.1844.PubMedPubMedCentralCrossRef

42.

Hansen CH, Krych L, Nielsen DS, Vogensen FK, Hansen LH, Sorensen SJ, et al. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Diabetologia. 2012;55(8):2285–94. doi:10.1007/s00125-012-2564-7.PubMedCrossRef

43.

Xu D, Prasad S, Miller SD. Inducing immune tolerance: a focus on type 1 diabetes mellitus. Diabetes Manag (Lond). 2013;3(5):415–26. doi:10.2217/dmt.13.36.CrossRef

44.

Michels AW, Eisenbarth GS. Immune intervention in type 1 diabetes. Semin Immunol. 2011;23(3):214–9. doi:10.1016/j.smim.2011.07.003.PubMedPubMedCentralCrossRef

45.

Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010;464(7293):1293–300.PubMedPubMedCentralCrossRef

46.

Luo X, Miller SD, Shea LD. Immune tolerance for autoimmune disease and cell transplantation. Annu Rev Biomed Eng. 2016;18:181–205. doi:10.1146/annurev-bioeng-110315-020137.PubMedPubMedCentralCrossRef

47.

Plesner A, Worsaae A, Dyrberg T, Gotfredsen C, Michelsen BK, Petersen JS. Immunization of diabetes-prone or non-diabetes-prone mice with GAD65 does not induce diabetes or islet cell pathology. J Autoimmun. 1998;11(4):335–41. doi:10.1006/jaut.1998.0206.PubMedCrossRef

48.

Uibo R, Lernmark A. GAD65 autoimmunity-clinical studies. Adv Immunol. 2008;100:39–78. doi:10.1016/S0065-2776(08)00803-1.PubMedCrossRef

49.

Agardh CD, Cilio CM, Lethagen A, Lynch K, Leslie RD, Palmer M, et al. Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes. J Diabetes Complicat. 2005;19(4):238–46. doi:10.1016/j.jdiacomp.2004.12.003.PubMedCrossRef

50.

Ludvigsson J, Faresjo M, Hjorth M, Axelsson S, Cheramy M, Pihl M, et al. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med. 2008;359(18):1909–20. doi:10.1056/NEJMoa0804328.PubMedCrossRef

51.

Ludvigsson J, Hjorth M, Cheramy M, Axelsson S, Pihl M, Forsander G, et al. Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial. Diabetologia. 2011;54(3):634–40. doi:10.1007/s00125-010-1988-1.PubMedCrossRef

52.

Cheramy M, Skoglund C, Johansson I, Ludvigsson J, Hampe CS, Casas R. GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response. Clin Immunol. 2010;137(1):31–40. doi:10.1016/j.clim.2010.06.001.PubMedCrossRef

53.

Wherrett DK, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet. 2011;378(9788):319–27. doi:10.1016/S0140-6736(11)60895-7.PubMedPubMedCentralCrossRef

54.

Harrison LC, Honeyman MC, Steele CE, Stone NL, Sarugeri E, Bonifacio E, et al. Pancreatic beta-cell function and immune responses to insulin after administration of intranasal insulin to humans at risk for type 1 diabetes. Diabetes Care. 2004;27(10):2348–55.PubMedCrossRef

55.

Fourlanos S, Perry C, Gellert SA, Martinuzzi E, Mallone R, Butler J, et al. Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes. Diabetes. 2011;60(4):1237–45. doi:10.2337/db10-1360.PubMedPubMedCentralCrossRef

56.

Skyler JS, Krischer JP, Wolfsdorf J, Cowie C, Palmer JP, Greenbaum C, et al. Effects of oral insulin in relatives of patients with type 1 diabetes: the diabetes prevention trial—type 1. Diabetes Care. 2005;28(5):1068–76.PubMedCrossRef

57.

Skyler JS, Greenbaum CJ, Lachin JM, Leschek E, Rafkin-Mervis L, Savage P, et al. Type 1 diabetes TrialNet—an international collaborative clinical trials network. Ann N Y Acad Sci. 2008;1150:14–24. doi:10.1196/annals.1447.054.PubMedPubMedCentralCrossRef

58.

Pozzilli P, Pitocco D, Visalli N, Cavallo MG, Buzzetti R, Crino A, et al. No effect of oral insulin on residual beta-cell function in recent-onset type I diabetes (the IMDIAB VII). IMDIAB group. Diabetologia. 2000;43(8):1000–4.PubMedCrossRef

59.

Fife BT, Guleria I, Gubbels Bupp M, Eagar TN, Tang Q, Bour-Jordan H, et al. Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway. J Exp Med. 2006;203(12):2737–47. doi:10.1084/jem.20061577.PubMedPubMedCentralCrossRef

60.

Daniel C, Weigmann B, Bronson R, von Boehmer H. Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope. J Exp Med. 2011;208(7):1501–10. doi:10.1084/jem.20110574.PubMedPubMedCentralCrossRef

61.

Judkowski V, Rodriguez E, Pinilla C, Masteller E, Bluestone JA, Sarvetnick N, et al. Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes. Clin Immunol. 2004;113(1):29–37. doi:10.1016/j.clim.2004.03.007.PubMedCrossRef

62.

Tarbell KV, Petit L, Zuo X, Toy P, Luo X, Mqadmi A, et al. Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J Exp Med. 2007;204(1):191–201. doi:10.1084/jem.20061631.PubMedPubMedCentralCrossRef

63.

Weber SE, Harbertson J, Godebu E, Mros GA, Padrick RC, Carson BD, et al. Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J Immunol. 2006;176(8):4730–9.PubMedCrossRef

64.

Jaeckel E, von Boehmer H, Manns MP. Antigen-specific FoxP3-transduced T-cells can control established type 1 diabetes. Diabetes. 2005;54(2):306–10.PubMedCrossRef

65.

• Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015;7(315):315ra189. doi:10.1126/scitranslmed.aad4134. Description of the use of Tregs for therapy of T1D. PubMedPubMedCentralCrossRef

66.

Xia CQ, Peng R, Qiu Y, Annamalai M, Gordon D, Clare-Salzler MJ. Transfusion of apoptotic beta-cells induces immune tolerance to beta-cell antigens and prevents type 1 diabetes in NOD mice. Diabetes. 2007;56(8):2116–23. doi:10.2337/db06-0825.PubMedCrossRef

67.

Marin-Gallen S, Clemente-Casares X, Planas R, Pujol-Autonell I, Carrascal J, Carrillo J, et al. Dendritic cells pulsed with antigen-specific apoptotic bodies prevent experimental type 1 diabetes. Clin Exp Immunol. 2010;160(2):207–14. doi:10.1111/j.1365-2249.2009.04082.x.PubMedPubMedCentralCrossRef

68.

Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF. Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol. 2008;38(5):1404–13. doi:10.1002/eji.200737984.PubMedCrossRef

69.

Fifis T, Gamvrellis A, Crimeen-Irwin B, Pietersz GA, Li J, Mottram PL, et al. Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J Immunol. 2004;173(5):3148–54.PubMedCrossRef

70.

Kourtis IC, Hirosue S, de Titta A, Kontos S, Stegmann T, Hubbell JA, et al. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice. PLoS One. 2013;8(4):e61646. doi:10.1371/journal.pone.0061646.PubMedPubMedCentralCrossRef

71.

Garciafigueroa Y, Trucco M, Giannoukakis N. A brief glimpse over the horizon for type 1 diabetes nanotherapeutics. Clin Immunol. 2015;160(1):36–45. doi:10.1016/j.clim.2015.03.016.PubMedCrossRef

72.

Shao K, Singha S, Clemente-Casares X, Tsai S, Yang Y, Santamaria P. Nanoparticle-based immunotherapy for cancer. ACS Nano. 2015;9(1):16–30. doi:10.1021/nn5062029.PubMedCrossRef

73.

Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, et al. Renal clearance of quantum dots. Nat Biotechnol. 2007;25(10):1165–70. doi:10.1038/nbt1340.PubMedPubMedCentralCrossRef

74.

Kwon YJ, Standley SM, Goh SL, Frechet JM. Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles. J Control Release. 2005;105(3):199–212. doi:10.1016/j.jconrel.2005.02.027.PubMedCrossRef

75.

Murthy N, Xu M, Schuck S, Kunisawa J, Shastri N, Frechet JM. A macromolecular delivery vehicle for protein-based vaccines: acid-degradable protein-loaded microgels. Proc Natl Acad Sci U S A. 2003;100(9):4995–5000. doi:10.1073/pnas.0930644100.PubMedPubMedCentralCrossRef

76.

Fromen CA, Robbins GR, Shen TW, Kai MP, Ting JP, DeSimone JM. Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization. Proc Natl Acad Sci U S A. 2015;112(2):488–93. doi:10.1073/pnas.1422923112.PubMedCrossRef

77.

Bal SM, Hortensius S, Ding Z, Jiskoot W, Bouwstra JA. Co-encapsulation of antigen and toll-like receptor ligand in cationic liposomes affects the quality of the immune response in mice after intradermal vaccination. Vaccine. 2011;29(5):1045–52. doi:10.1016/j.vaccine.2010.11.061.PubMedCrossRef

78.

Koppolu B, Zaharoff DA. The effect of antigen encapsulation in chitosan particles on uptake, activation and presentation by antigen presenting cells. Biomaterials. 2013;34(9):2359–69. doi:10.1016/j.biomaterials.2012.11.066.PubMedCrossRef

79.

Lockman PR, Koziara JM, Mumper RJ, Allen DD. Nanoparticle surface charges alter blood-brain barrier integrity and permeability. J Drug Target. 2004;12(9–10):635–41. doi:10.1080/10611860400015936.PubMedCrossRef

80.

Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener JW, et al. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J Control Release. 2000;65(1–2):133–48.PubMedCrossRef

81.

Pensado A, Fernandez-Pineiro I, Seijo B, Sanchez A. Anionic nanoparticles based on span 80 as low-cost, simple and efficient non-viral gene-transfection systems. Int J Pharm. 2014;476(1–2):23–30. doi:10.1016/j.ijpharm.2014.09.032.PubMedCrossRef

82.

Ruenraroengsak P, Tetley TD. Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells. Part Fibre Toxicol. 2015;12:19. doi:10.1186/s12989-015-0091-7.PubMedPubMedCentralCrossRef

83.

Liu Y, Li W, Lao F, Liu Y, Wang L, Bai R, et al. Intracellular dynamics of cationic and anionic polystyrene nanoparticles without direct interaction with mitotic spindle and chromosomes. Biomaterials. 2011;32(32):8291–303. doi:10.1016/j.biomaterials.2011.07.037.PubMedCrossRef

84.

Tagalakis AD, Lee DH, Bienemann AS, Zhou H, Munye MM, Saraiva L, et al. Multifunctional, self-assembling anionic peptide-lipid nanocomplexes for targeted siRNA delivery. Biomaterials. 2014;35(29):8406–15. doi:10.1016/j.biomaterials.2014.06.003.PubMedCrossRef

85.

Sun Y, Guo F, Zou Z, Li C, Hong X, Zhao Y, et al. Cationic nanoparticles directly bind angiotensin-converting enzyme 2 and induce acute lung injury in mice. Part Fibre Toxicol. 2015;12:4. doi:10.1186/s12989-015-0080-x.PubMedPubMedCentralCrossRef

86.

Yang SH, Heo D, Park J, Na S, Suh JS, Haam S, et al. Role of surface charge in cytotoxicity of charged manganese ferrite nanoparticles towards macrophages. Nanotechnology. 2012;23(50):505702. doi:10.1088/0957-4484/23/50/505702.PubMedCrossRef

87.

Chao Y, Makale M, Karmali PP, Sharikov Y, Tsigelny I, Merkulov S, et al. Recognition of dextran-superparamagnetic iron oxide nanoparticle conjugates (Feridex) via macrophage scavenger receptor charged domains. Bioconjug Chem. 2012;23(5):1003–9. doi:10.1021/bc200685a.PubMedPubMedCentralCrossRef

88.

Champion JA, Mitragotri S. Role of target geometry in phagocytosis. Proc Natl Acad Sci U S A. 2006;103(13):4930–4. doi:10.1073/pnas.0600997103.PubMedPubMedCentralCrossRef

89.

Verma A, Uzun O, Hu Y, Hu Y, Han HS, Watson N, et al. Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nat Mater. 2008;7(7):588–95. doi:10.1038/nmat2202.PubMedPubMedCentralCrossRef

90.

Stone JW, Thornburg NJ, Blum DL, Kuhn SJ, Wright DW, Crowe JE Jr. Gold nanorod vaccine for respiratory syncytial virus. Nanotechnology. 2013;24(29):295102. doi:10.1088/0957-4484/24/29/295102.PubMedPubMedCentralCrossRef

91.

Karch CP, Li J, Kulangara C, Paulillo SM, Raman SK, Emadi S, et al. Vaccination with self-adjuvanted protein nanoparticles provides protection against lethal influenza challenge. Nanomedicine. 2017;13(1):241–51. doi:10.1016/j.nano.2016.08.030.PubMedCrossRef

92.

Doll TA, Neef T, Duong N, Lanar DE, Ringler P, Muller SA, et al. Optimizing the design of protein nanoparticles as carriers for vaccine applications. Nanomedicine. 2015;11(7):1705–13. doi:10.1016/j.nano.2015.05.003.PubMedPubMedCentralCrossRef

93.

Babapoor S, Neef T, Mittelholzer C, Girshick T, Garmendia A, Shang H, et al. A novel vaccine using nanoparticle platform to present immunogenic M2e against avian influenza infection. Influenza Res Treat. 2011;2011:126794. doi:10.1155/2011/126794.PubMed

94.

Wahome N, Pfeiffer T, Ambiel I, Yang Y, Keppler OT, Bosch V, et al. Conformation-specific display of 4E10 and 2F5 epitopes on self-assembling protein nanoparticles as a potential HIV vaccine. Chem Biol Drug Des. 2012;80(3):349–57. doi:10.1111/j.1747-0285.2012.01423.x.PubMedCrossRef

95.

Monopoli MP, Aberg C, Salvati A, Dawson KA. Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol. 2012;7(12):779–86. doi:10.1038/nnano.2012.207.PubMedCrossRef

96.

Tenzer S, Docter D, Kuharev J, Musyanovych A, Fetz V, Hecht R, et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat Nanotechnol. 2013;8(10):772–81. doi:10.1038/nnano.2013.181.PubMedCrossRef

97.

Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci U S A. 2008;105(38):14265–70. doi:10.1073/pnas.0805135105.PubMedPubMedCentralCrossRef

98.

• Smarr CB, Yap WT, Neef TP, Pearson RM, Hunter ZN, Ifergan I, et al. Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization. Proc Natl Acad Sci USA. 2016;113(18):5059–64. doi:10.1073/pnas.1505782113. Demonstration that infusion of antigen-encapsulating PLG nanoparticles induce tolerance in Th2 cells useful in prevention and treatment in an animal model of allergic airway disease. PubMedPubMedCentralCrossRef

99.

Ilinskaya AN, Dobrovolskaia MA. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials. Br J Pharmacol. 2014;171(17):3988–4000. doi:10.1111/bph.12722.PubMedPubMedCentralCrossRef

100.

Phillips B, Nylander K, Harnaha J, Machen J, Lakomy R, Styche A, et al. A microsphere-based vaccine prevents and reverses new-onset autoimmune diabetes. Diabetes. 2008;57(6):1544–55. doi:10.2337/db07-0507.PubMedPubMedCentralCrossRef

101.

Leuschner F, Dutta P, Gorbatov R, Novobrantseva TI, Donahoe JS, Courties G, et al. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol. 2011;29(11):1005–10. doi:10.1038/nbt.1989.PubMedPubMedCentralCrossRef

102.

Wang P, Yigit MV, Ran C, Ross A, Wei L, Dai G, et al. A theranostic small interfering RNA nanoprobe protects pancreatic islet grafts from adoptively transferred immune rejection. Diabetes. 2012;61(12):3247–54. doi:10.2337/db12-0441.PubMedPubMedCentralCrossRef

103.

Shah M, Edman MC, Janga SR, Shi P, Dhandhukia J, Liu S, et al. A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjogren’s syndrome. J Control Release. 2013;171(3):269–79. doi:10.1016/j.jconrel.2013.07.016.PubMedPubMedCentralCrossRef

104.

Tsai S, Shameli A, Yamanouchi J, Clemente-Casares X, Wang J, Serra P, et al. Reversal of autoimmunity by boosting memory-like autoregulatory T cells. Immunity. 2010;32(4):568–80. doi:10.1016/j.immuni.2010.03.015.PubMedCrossRef

105.

•• Clemente-Casares X, Blanco J, Ambalavanan P, Yamanouchi J, Singha S, Fandos C, et al. Expanding antigen-specific regulatory networks to treat autoimmunity. Nature. 2016;530(7591):434–40. doi:10.1038/nature16962. Demonstration that iron oxide nanoparticles expressing peptide-MHC molecules can induce tolerance for treatment of autoimmune disease. PubMedCrossRef

106.

Singha S, Shao K, Yang Y, Clemente-Casares X, Sole P, Clemente A, et al. Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices. Nat Nanotechnol. 2017; doi:10.1038/nnano.2017.56.

107.

Schutz C, Fleck M, Mackensen A, Zoso A, Halbritter D, Schneck JP, et al. Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells. Blood. 2008;111(7):3546–52. doi:10.1182/blood-2007-09-113522.PubMedPubMedCentralCrossRef

108.

Schutz C, Fleck M, Schneck JP, Oelke M. Killer artificial antigen presenting cells (KaAPC) for efficient in vitro depletion of human antigen-specific T cells. J Vis Exp. 2014;90:e51859. doi:10.3791/51859.

109.

Maldonado RA, LaMothe RA, Ferrari JD, Zhang AH, Rossi RJ, Kolte PN, et al. Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance. Proc Natl Acad Sci U S A. 2015;112(2):E156–65. doi:10.1073/pnas.1408686111.PubMedCrossRef

110.

Zhang AH, Rossi RJ, Yoon J, Wang H, Scott DW. Tolerogenic nanoparticles to induce immunologic tolerance: prevention and reversal of FVIII inhibitor formation. Cell Immunol. 2016;301:74–81. doi:10.1016/j.cellimm.2015.11.004.PubMedCrossRef

111.

Yeste A, Nadeau M, Burns EJ, Weiner HL, Quintana FJ. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2012;109(28):11270–5. doi:10.1073/pnas.1120611109.PubMedPubMedCentralCrossRef

112.

•• Yeste A, Takenaka MC, Mascanfroni ID, Nadeau M, Kenison JE, Patel B, et al. Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Sci Signal. 2016;9(433):ra61. doi:10.1126/scisignal.aad0612. Demonstration that gold nanoparticles expressing antigen and an AhR agonist can prevent development of T1D in NOD mice. PubMedCrossRef

113.

Macauley MS, Pfrengle F, Rademacher C, Nycholat CM, Gale AJ, von Drygalski A, et al. Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis. J Clin Invest. 2013;123(7):3074–83. doi:10.1172/JCI69187.PubMedPubMedCentralCrossRef

114.

Pfrengle F, Macauley MS, Kawasaki N, Paulson JC. Copresentation of antigen and ligands of Siglec-G induces B cell tolerance independent of CD22. J Immunol. 2013;191(4):1724–31. doi:10.4049/jimmunol.1300921.PubMedPubMedCentralCrossRef

115.

Copp JA, Fang RH, Luk BT, Hu CM, Gao W, Zhang K, et al. Clearance of pathological antibodies using biomimetic nanoparticles. Proc Natl Acad Sci U S A. 2014;111(37):13481–6. doi:10.1073/pnas.1412420111.PubMedPubMedCentralCrossRef

116.

•• Getts DR, Martin AJ, DP MC, Terry RL, Hunter ZN, Yap WT, et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nat Biotechnol. 2012;30(12):1217–24. doi:10.1038/nbt.2434. Initial description that antigen coupled to polystyrene and PLG nanoparticles can induce tolerance active in prevention of EAE. PubMedPubMedCentralCrossRef

117.

•• Hunter Z, DP MC, Yap WT, Harp CT, Getts DR, Shea LD, et al. A biodegradable nanoparticle platform for the induction of antigen-specific immune tolerance for treatment of autoimmune disease. ACS Nano. 2014;8(3):2148–60. doi:10.1021/nn405033r. Description of the ability of antigen-coupled PLG nanoparticles to treat ongoing EAE. PubMedPubMedCentralCrossRef

118.

•• McCarthy DP, Yap JW, Harp CT, Song WK, Chen J, Pearson RM, et al. An antigen-encapsulating nanoparticle platform for TH1/17 immune tolerance therapy. Nanomedicine. 2017;13(1):191–200. doi:10.1016/j.nano.2016.09.007. Description of the ability of antigen-encapsulating PLG nanoparticles to prevent and treat EAE.

119.

• Hlavaty KA, DP MC, Saito E, Yap WT, Miller SD, Shea LD. Tolerance induction using nanoparticles bearing HY peptides in bone marrow transplantation. Biomaterials. 2016;76:1–10. doi:10.1016/j.biomaterials.2015.10.041. Description of the ability of either antigen-coupled or antigen encapsulating nanoparticles to prevent bone marrow transplant rejection.

120.

•• Miller SD, Prasad S, Neef T. Antigen-encapsulating PLG nanoparticles induce long-lived regulatory T cell control of activated diabetogenic CD4 and CD8 T cells (Abstract). Immunology of Diabetes Society 15th International Congress. 2017. Demonstration of nanoparticle tolerance for the treatment of adoptive transfer models of T1D.

121.

• Bryant J, Hlavaty KA, Zhang X, Yap WT, Zhang L, Shea LD, et al. Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation. Biomaterials. 2014;35(31):8887–94. doi:10.1016/j.biomaterials.2014.06.044. Demonstration that antigen-coupled nanoparticles can induce tolerance to protect transplanted allogeneic islets. PubMedPubMedCentralCrossRef

122.

Hlavaty KA, Luo X, Shea LD, Miller SD. Cellular and molecular targeting for nanotherapeutics in transplantation tolerance. Clin Immunol. 2015;160(1):14–23. doi:10.1016/j.clim.2015.03.013.PubMedPubMedCentralCrossRef

123.

Chopra S, Bertrand N, Lim JM, Wang A, Farokhzad OC, Karnik R. Design of insulin-loaded nanoparticles enabled by multistep control of nanoprecipitation and zinc chelation. ACS Appl Mater Interfaces. 2017;9(13):11440–50. doi:10.1021/acsami.6b16854.PubMedCrossRef

124.

• Luo X, Pothoven KL, McCarthy D, DeGutes M, Martin A, Getts DR, et al. ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms. Proc Natl Acad Sci U S A. 2008;105(38):14527–32. doi:10.1073/pnas.0805204105. Description of the ability of tolerance induced by the i.v. infusion of apoptotic donor leukocytes to long-term survival of transplanted donor islets. PubMedPubMedCentralCrossRef

125.

Desai T, Shea LD. Advances in islet encapsulation technologies. Nat Rev Drug Discov. 2016; doi:10.1038/nrd.2016.232.

Title: Tolerogenic Nanoparticles to Treat Islet Autoimmunity
Authors: Tobias Neef
Stephen D. Miller
Publication date: 01-10-2017
Publisher: Springer US
Published in: Current Diabetes Reports / Issue 10/2017
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-017-0914-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 10/2017

Intraocular Inflammation in Diabetic Populations

New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin

Multivariable Adaptive Artificial Pancreas System in Type 1 Diabetes

Weight Management in Patients with Type 1 Diabetes and Obesity

Diabetic Eye Screening: Knowledge and Perspectives from Providers and Patients

The Effects of Chronic Aerobic Exercise on Cardiovascular Risk Factors in Persons with Diabetes Mellitus

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials