An epicutaneous therapeutic pollen-allergen extract delivery system in an allergic rhinitis mouse model: based on allergen loading on DC-specific aptamers conjugated nanogolds.
Allergic rhinitis
Aptamer
Epicutaneous immunotherapy
Gold nanoparticles
Pollen allergy
Skin penetrating peptide
Journal
Immunologic research
ISSN: 1559-0755
Titre abrégé: Immunol Res
Pays: United States
ID NLM: 8611087
Informations de publication
Date de publication:
13 Dec 2023
13 Dec 2023
Historique:
received:
17
10
2023
accepted:
30
11
2023
medline:
13
12
2023
pubmed:
13
12
2023
entrez:
13
12
2023
Statut:
aheadofprint
Résumé
Gold nanoparticles (GNPs) have previously been suggested as appropriate carriers for allergen-specific immunotherapy (AIT). In this study, we assessed efficacy of GNPs and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and non-allergenic components. BALB/c mice were sensitized to the total protein extract of Platanus orientalis pollen and epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, total extract loaded GNPs, and total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). Then, the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and mixture of recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue were evaluated. This study indicated the total extract-loaded GNPs, especially Pla. ext (50 μg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, the histopathological analysis of lung tissue showed a significant decrease in allergic inflammation and histopathological damage. The DC-targeted group revealed the most significant improvement in allergic-related immune factors with no histopathological damage compared with the same dose without aptamer. Loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in a pollen-induced allergic mouse model.
Sections du résumé
BACKGROUND
BACKGROUND
Gold nanoparticles (GNPs) have previously been suggested as appropriate carriers for allergen-specific immunotherapy (AIT). In this study, we assessed efficacy of GNPs and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and non-allergenic components.
METHODS
METHODS
BALB/c mice were sensitized to the total protein extract of Platanus orientalis pollen and epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, total extract loaded GNPs, and total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). Then, the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and mixture of recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue were evaluated.
RESULTS
RESULTS
This study indicated the total extract-loaded GNPs, especially Pla. ext (50 μg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, the histopathological analysis of lung tissue showed a significant decrease in allergic inflammation and histopathological damage. The DC-targeted group revealed the most significant improvement in allergic-related immune factors with no histopathological damage compared with the same dose without aptamer.
CONCLUSION
CONCLUSIONS
Loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in a pollen-induced allergic mouse model.
Identifiants
pubmed: 38091227
doi: 10.1007/s12026-023-09445-6
pii: 10.1007/s12026-023-09445-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Pohlit H, Bellinghausen I, Frey H, Saloga J. Recent advances in the use of nanoparticles for allergen-specific immunotherapy. Allergy. 2017;72(10):1461–74.
pubmed: 28474379
doi: 10.1111/all.13199
Wang XY, Ma TT, Wang XY, Zhuang Y, Wang XD, Ning HY, et al. Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China. Allergy. 2018;73(6):1232–43.
pubmed: 29322523
doi: 10.1111/all.13388
Larsson O, Hellkvist L, Peterson-Westin U, Cardell LO. Novel strategies for the treatment of grass pollen-induced allergic rhinitis. Expert Opin Biol Ther. 2016;16(9):1143–50.
pubmed: 27269991
doi: 10.1080/14712598.2016.1190829
McDonell AL, Wahn U, Demuth D, Richards C, Hawes C, Andreasen JN, et al. Allergy immunotherapy prescribing trends for grass pollen-induced allergic rhinitis in Germany: a retrospective cohort analysis. Allergy Asthma Clin Immunol. 2015;11(1):1–7.
doi: 10.1186/s13223-015-0085-x
Durham SR, Penagos M. Sublingual or subcutaneous immunotherapy for allergic rhinitis? J Allergy Clin Immunol. 2016;137(2):339–49. e10
pubmed: 26853126
doi: 10.1016/j.jaci.2015.12.1298
Cox L, Calderon MA. Subcutaneous specific immunotherapy for seasonal allergic rhinitis: a review of treatment practices in the US and Europe. Curr Med Res Opin. 2010;26(12):2723–33.
pubmed: 20979432
doi: 10.1185/03007995.2010.528647
Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1):S1–S55.
pubmed: 21122901
doi: 10.1016/j.jaci.2010.09.034
Bousquet J, Lockey R, Malling H-J. Allergen immunotherapy: therapeutic vaccines for allergic diseases A WHO position paper. J Allergy Clin Immunol. 1998;102(4):558–62.
pubmed: 9802362
doi: 10.1016/S0091-6749(98)70271-4
Senti G, von Moos S, Kündig TM. Epicutaneous immunotherapy for aeroallergen and food allergy. Current treatment options in allergy. 2014;1:68–78.
pubmed: 24918342
doi: 10.1007/s40521-013-0003-8
Senti G, von Moos S, Tay F, Graf N, Sonderegger T, Johansen P, et al. Epicutaneous allergen-specific immunotherapy ameliorates grass pollen–induced rhinoconjunctivitis: a double-blind, placebo-controlled dose escalation study. J Allergy Clin Immunol. 2012;129(1):128–35.
pubmed: 21996342
doi: 10.1016/j.jaci.2011.08.036
Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Puteaux E, Dupont C, et al. Epicutaneous immunotherapy compared with sublingual immunotherapy in mice sensitized to pollen (Phleum pratense). Int Scholarly Res Not. 2012;2012:375735.
Koushki K, Varasteh A-R, Shahbaz SK, Sadeghi M, Mashayekhi K, Ayati SH, et al. Dc-specific aptamer decorated gold nanoparticles: a new attractive insight into the nanocarriers for allergy epicutaneous immunotherapy. Int J Pharm. 2020;584:119403.
pubmed: 32387307
doi: 10.1016/j.ijpharm.2020.119403
Wang Y, Kong Y, Wu MX. Innovative systems to deliver allergen powder for epicutaneous immunotherapy. Front Immunol. 2021;12:647954.
pubmed: 33841430
pmcid: 8033039
doi: 10.3389/fimmu.2021.647954
Korotchenko E, Schießl V, Scheiblhofer S, Schubert M, Dall E, Joubert IA, et al. Laser-facilitated epicutaneous immunotherapy with hypoallergenic beta-glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma. Allergy. 2021;76(1):210–22.
pubmed: 32621318
doi: 10.1111/all.14481
Nesovic LD, Shakya AK, Gill HS. Treating allergies via skin–recent advances in cutaneous allergen immunotherapy. Adv Drug Deliv Rev. 2022;190:114458.
Landers JJ, Janczak KW, Shakya AK, Zarnitsyn V, Patel SR, Baker JR Jr, et al. Targeted allergen-specific immunotherapy within the skin improves allergen delivery to induce desensitization to peanut. Immunotherapy. 2022;14(7):539–52.
pubmed: 35196877
pmcid: 9043875
doi: 10.2217/imt-2021-0206
Rani D, Nayak B, Srivastava S. Immunogenicity of gold nanoparticle-based truncated ORF2 vaccine in mice against Hepatitis E virus. 3 Biotech. 2021;11:1–11.
doi: 10.1007/s13205-020-02573-y
Chen Y, Feng X. Gold nanoparticles for skin drug delivery. Int J Pharm. 2022;18:122122.
Ko W-C, Wang S-J, Hsiao C-Y, Hung C-T, Hsu Y-J, Chang D-C, et al. Pharmacological role of functionalized gold nanoparticles in disease applications. Molecules. 2022;27(5):1551.
pubmed: 35268651
pmcid: 8911979
doi: 10.3390/molecules27051551
Catuogno S, Esposito CL, De Franciscis V. Aptamer-mediated targeted delivery of therapeutics: an update. Pharmaceuticals. 2016;9(4):69.
pubmed: 27827876
pmcid: 5198044
doi: 10.3390/ph9040069
Moghadam M, Sankian M, Abnous K, Varasteh A, Taghdisi S, Mahmoudi M, et al. Cell-SELEX-based selection and characterization of a G-quadruplex DNA aptamer against mouse dendritic cells. Int Immunopharmacol. 2016;36:324–32.
pubmed: 27232653
doi: 10.1016/j.intimp.2016.04.042
Shahbaz SK, Varasteh A-R, Koushki K, Ayati SH, Mashayekhi K, Sadeghi M, et al. Sublingual dendritic cells targeting by aptamer: Possible approach for improvement of sublingual immunotherapy efficacy. Int Immunopharmacol. 2020;85:106603.
doi: 10.1016/j.intimp.2020.106603
Ganji A, Varasteh A, Sankian M. Aptamers: new arrows to target dendritic cells. J Drug Target. 2016;24(1):1–12.
pubmed: 25950603
doi: 10.3109/1061186X.2015.1041962
Zheng L, Wu H, Wen N, Zhang Y, Wang Z, Peng X, et al. Aptamer-functionalized nanovaccines: targeting in vivo DC subsets for enhanced antitumor immunity. ACS Appl Mater Interfaces. 2023;15(15):18590–7.
Wengerter BC, Katakowski JA, Rosenberg JM, Park CG, Almo SC, Palliser D, et al. Aptamer-targeted antigen delivery. Mol Ther. 2014;22(7):1375–87.
pubmed: 24682172
pmcid: 4089008
doi: 10.1038/mt.2014.51
Sadeghi M, Koushki K, Mashayekhi K, Ayati SH, Shahbaz SK, Moghadam M, et al. DC-targeted gold nanoparticles as an efficient and biocompatible carrier for modulating allergic responses in sublingual immunotherapy. Int Immunopharmacol. 2020;86:106690.
pubmed: 32585607
doi: 10.1016/j.intimp.2020.106690
Pazouki N, Sankian M, Nejadsattari T, Khavari-Nejad R-A, Varasteh A-R, editors. Oriental plane pollen allergy: identification of allergens and cross-reactivity between relevant species. Allergy Asthma Proc. 2008;29(6):622–8
Varasteh A-R. Complementary DNA cloning and immunologic characterization of a new Platanus orientalis pollen allergen, Pla or 1.0101 Nazanin Pazouki, Mojtaba Sankian, Taher Nejadsattari, Ramezan-Ali Khavari-Nejad. Res J Biol Sci. 2008;3(12):1419–25.
Sedghy F, Sankian M, Moghadam M, Varasteh A-R. Quantification of Pla or 3, a Platanus orientalis allergen, grown under different environmental conditions, by sandwich ELISA. Rep Biochem Mol Biol. 2016;5(1):40.
pubmed: 28070533
pmcid: 5214682
Sankian M, Vahedi F, Pazouki N, Moghadam M, Azad FJ, Varasteh A-R. Cloning and expression of cyclophilin from Platanus orientalis pollens in Escherichia coli. Rep Biochem Mol Biol. 2012;1(1):25.
pubmed: 26989705
pmcid: 4757077
Pong B-K, Elim HI, Chong J-X, Ji W, Trout BL, Lee J-Y. New insights on the nanoparticle growth mechanism in the citrate reduction of gold (III) salt: formation of the Au nanowire intermediate and its nonlinear optical properties. J Phys Chem C. 2007;111(17):6281–7.
doi: 10.1021/jp068666o
Kim D, Jeong YY, Jon S. A drug-loaded aptamer− gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano. 2010;4(7):3689–96.
pubmed: 20550178
doi: 10.1021/nn901877h
Hajavi J, Hashemi M, Sankian M. Evaluation of size and dose effects of rChe a 3 allergen loaded PLGA nanoparticles on modulation of Th2 immune responses by sublingual immunotherapy in mouse model of rhinitis allergic. Int J Pharm. 2019;563:282–92.
pubmed: 30902708
doi: 10.1016/j.ijpharm.2019.03.040
Sonavane G, Tomoda K, Sano A, Ohshima H, Terada H, Makino K. In vitro permeation of gold nanoparticles through rat skin and rat intestine: effect of particle size. Colloids Surf B Biointerfaces. 2008;65(1):1–10.
pubmed: 18499408
doi: 10.1016/j.colsurfb.2008.02.013
Gopinath K, Gowri S, Karthika V, Arumugam A. Green synthesis of gold nanoparticles from fruit extract of Terminalia arjuna, for the enhanced seed germination activity of Gloriosa superba. J Nanostruct Chem. 2014;4:1–11.
doi: 10.1007/s40097-014-0115-0
He YQ, Liu SP, Kong L, Liu ZF. A study on the sizes and concentrations of gold nanoparticles by spectra of absorption, resonance Rayleigh scattering and resonance non-linear scattering. Spectrochim Acta A Mol Biomol Spectrosc. 2005;61(13-14):2861–6.
pubmed: 16165025
doi: 10.1016/j.saa.2004.10.035
Peng L, Liang Y, Zhong X, Liang Z, Tian Y, Li S, et al. Aptamer-conjugated gold nanoparticles targeting epidermal growth factor receptor variant III for the treatment of glioblastoma. Int J Nanomedicine. 2020;1363–72
Kim J, Anthony MY, Kubelick KP, Emelianov SY. Gold nanoparticles conjugated with DNA aptamer for photoacoustic detection of human matrix metalloproteinase-9. Photoacoustics. 2022;25:100307.
pubmed: 34703762
doi: 10.1016/j.pacs.2021.100307
Raju G, Katiyar N, Vadukumpully S, Shankarappa SA. Penetration of gold nanoparticles across the stratum corneum layer of thick-Skin. J Dermatol Sci. 2018;89(2):146–54.
pubmed: 29154084
doi: 10.1016/j.jdermsci.2017.11.001
Barreto E, Serra MF, Dos Santos RV, Dos Santos CEA, Hickmann J, Cotias AC, et al. Local administration of gold nanoparticles prevents pivotal pathological changes in murine models of atopic asthma. J Biomed Nanotechnol. 2015;11(6):1038–50.
pubmed: 26353593
doi: 10.1166/jbn.2015.2024
Uchiyama MK, Deda DK, Rodrigues SFP, Drewes CC, Bolonheis SM, Kiyohara PK, et al. In vivo and in vitro toxicity and anti-inflammatory properties of gold nanoparticle bioconjugates to the vascular system. Toxicol Sci. 2014;142(2):497–507.
pubmed: 25260831
doi: 10.1093/toxsci/kfu202
Tsai CY, Shiau AL, Chen SY, Chen YH, Cheng PC, Chang MY, et al. Amelioration of collagen-induced arthritis in rats by nanogold. Arthritis Rheum: Official J American Coll Rheumatol. 2007;56(2):544–54.
doi: 10.1002/art.22401
Khan MA, Khan MJ. Nano-gold displayed anti-inflammatory property via NF-kB pathways by suppressing COX-2 activity. Artif Cells, Nanomed Biotechnol. 2018;46(sup1):1149–58.
pubmed: 29553845
doi: 10.1080/21691401.2018.1446968
dos Santos Haupenthal DP, Mendes C, de Bem SG, Zaccaron RP, Corrêa MEAB, Nesi RT, et al. Effects of treatment with gold nanoparticles in a model of acute pulmonary inflammation induced by lipopolysaccharide. J Biomed Mater Res A. 2020;108(1):103–15.
pubmed: 31502356
doi: 10.1002/jbm.a.36796
Chen H, Dorrigan A, Saad S, Hare DJ, Cortie MB, Valenzuela SM. In vivo study of spherical gold nanoparticles: inflammatory effects and distribution in mice. PloS One. 2013;8(2):e58208.
pubmed: 23469154
pmcid: 3585265
doi: 10.1371/journal.pone.0058208
Rizwan H, Mohanta J, Si S, Pal A. Gold nanoparticles reduce high glucose-induced oxidative-nitrosative stress regulated inflammation and apoptosis via tuberin-mTOR/NF-κB pathways in macrophages. Int J Nanomed. 2017;12:5841.
doi: 10.2147/IJN.S141839
Hussein RM, Saleh H. Promising therapeutic effect of gold nanoparticles against dinitrobenzene sulfonic acid-induced colitis in rats. Nanomedicine. 2018;13(14):1657–79.
pubmed: 30085904
doi: 10.2217/nnm-2018-0009
Brimnes J, Kildsgaard J, Jacobi H, Lund K. Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis. Clin Exp Allergy. 2007;37(4):488–97.
pubmed: 17430344
doi: 10.1111/j.1365-2222.2006.02624.x
Van Rijt LS, Gouveia L, Logiantara A, Canbaz D, Opstelten D-J, Van Der Kleij HP, et al. Birch pollen immunotherapy in mice: inhibition of Th2 inflammation is not sufficient to decrease airway hyper-reactivity. Int Arch Allergy Immunol. 2014;165(2):128–39.
pubmed: 25412572
doi: 10.1159/000368777
Sampson HA, Shreffler WG, Yang WH, Sussman GL, Brown-Whitehorn TF, Nadeau KC, et al. Effect of varying doses of epicutaneous immunotherapy vs placebo on reaction to peanut protein exposure among patients with peanut sensitivity: a randomized clinical trial. Jama. 2017;318(18):1798–809.
pubmed: 29136445
pmcid: 5820709
doi: 10.1001/jama.2017.16591
Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Dupont C, Benhamou PH. Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy. 2010;40(4):659–67.
pubmed: 20002446
doi: 10.1111/j.1365-2222.2009.03430.x
Mondoulet L, Dioszeghy V, Puteaux E, Ligouis M, Dhelft V, Plaquet C, et al. Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model. J Allergy Clin Immunol. 2015;135(6):1546-57. e4.
Dioszeghy V, Mondoulet L, Laoubi L, Dhelft V, Plaquet C, Bouzereau A, et al. Antigen uptake by Langerhans cells is required for the induction of regulatory T cells and the acquisition of tolerance during epicutaneous immunotherapy in OVA-sensitized mice. Front Immunol. 2018;9:1951.
pubmed: 30233572
pmcid: 6129590
doi: 10.3389/fimmu.2018.01951
Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Benhamou P-H, et al. Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice. J Immunol. 2011;186(10):5629–37.
pubmed: 21490160
doi: 10.4049/jimmunol.1003134
Mondoulet L, Dioszeghy V, Larcher T, Ligouis M, Dhelft V, Puteaux E, et al. Epicutaneous immunotherapy (EPIT) blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice. PloS One. 2012;7(2):e31967.
pubmed: 22363776
pmcid: 3283696
doi: 10.1371/journal.pone.0031967
Tordesillas L, Mondoulet L, Blazquez AB, Benhamou P-H, Sampson HA, Berin MC. Epicutaneous immunotherapy induces gastrointestinal LAP+ regulatory T cells and prevents food-induced anaphylaxis. J Allergy Clin Immunol. 2017;139(1):189-201. e4.
pubmed: 27417020
doi: 10.1016/j.jaci.2016.03.057
Lin AY, Lunsford J, Bear AS, Young JK, Eckels P, Luo L, et al. High-density sub-100-nm peptide-gold nanoparticle complexes improve vaccine presentation by dendritic cells in vitro. Nanoscale Res Lett. 2013;8:1–11.
doi: 10.1186/1556-276X-8-72
Ahn S, Lee IH, Kang S, Kim D, Choi M, Saw PE, et al. Gold nanoparticles displaying tumor-associated self-antigens as a potential vaccine for cancer immunotherapy. Adv Healthc Mater. 2014;3(8):1194–9.
pubmed: 24652754
doi: 10.1002/adhm.201300597
Liu G, Liu M, Wang J, Mou Y, Che H. The role of regulatory T cells in epicutaneous immunotherapy for food allergy. Front Immunol. 2021;12:660974.
pubmed: 34305893
pmcid: 8297384
doi: 10.3389/fimmu.2021.660974
Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, et al. The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice. Clin Exp Allergy. 2014;44(6):867–81.
pubmed: 24666588
pmcid: 4233996
doi: 10.1111/cea.12312
Mondoulet L, Dioszeghy V, Puteaux E, Ligouis M, Dhelft V, Letourneur F, et al. Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice. Clin Transl Allergy. 2012;2(1):1–12.
doi: 10.1186/2045-7022-2-22
Choi BS. Is determining nasal eosinophil count and nasal eosinophil peroxidase concentration clinically useful in children with rhinits? Korean J Pediatr. 2019;62(9):342–3.
pubmed: 31319644
pmcid: 6753316
doi: 10.3345/kjp.2019.00556
Pawankar R, Mori S, Ozu C, Kimura S. Overview on the pathomechanisms of allergic rhinitis. Asia Pac Allergy. 2011;1(3):157–67.
pubmed: 22053313
pmcid: 3206239
doi: 10.5415/apallergy.2011.1.3.157
Chen Y, Yang M, Deng J, Wang K, Shi J, Sun Y. Elevated levels of activated and pathogenic eosinophils characterize moderate-severe house dust mite allergic rhinitis. J Immunol Res. 2020;2020:8085615
Salari F, Varasteh A-R, Vahedi F, Hashemi M, Sankian M. Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice. Int Immunopharmacol. 2015;29(2):672–8.
pubmed: 26404189
doi: 10.1016/j.intimp.2015.09.011