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Mediterranean Journal of Medicine and Medical Sciences
https://mmj.org.ly/article/doi/10.5281/zenodo.16117843

Mediterranean Journal of Medicine and Medical Sciences

REVIEW

Targeted nano-constructs for the treatment of autoimmune diseases: A comprehensive review of advances, mechanisms, and clinical potential

Ramdas Bhat, Sinchana S Bhat

http://dx.doi.org/10.5281/zenodo.16117843 Mediterr J Med Med Sci, vol.1, n2, p.8-16, 2025
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Abstract

Autoimmune diseases are chronic, disabling disorders that involve immune system dysfunction and recognition of self-antigens and lead to progressive tissue injury. Afflecting about 5.0-10.0% of the world's population. Autoimmune diseases like rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and type 1 diabetes are a major health burden. Traditional treatments, such as corticosteroids, disease-modifying antirheumatic drugs, and biologics, are not antigen-specific and have systemic immune suppression, incomplete remission, and chronic side effects. Targeted nanoconstructs, which involve nanoparticles designed for the targeted delivery of therapeutic agents, represent a revolutionary strategy through the amplification of bioavailability, optimization of immune modulation, and reduction of off-target toxicity. These nanosystems can deliver autoantigens or immunosuppressive drugs to target immune cells or tissues, thus restoring tolerance and suppressing inflammation. Here, we give a broad overview of nanoconstruct-based approaches for treating autoimmune diseases in this review. This review describes the design principles behind nanoconstructs, including surface functionalization, materials, and routes of delivery, and reviews how these constructs regulate innate and adaptive immune responses. In addition, it emphasizes recent clinical uses, illustrated with examples from rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and type 1 diabetes, and discusses essential translational issues such as safety, scalability, regulatory hurdles, and disease heterogeneity. It is also discussing emerging trends in personalized nanomedicine, theranostics, and artificial intelligence-guided design. Together, these technologies poistion nanoconstructs as a promising next-generation platform for the effective, targeted, and individualized treatment of autoimmune diseases.

Keywords

Autoimmune diseases, drug delivery, immune tolerance, nanoparticles, nanomedicine targeted nanoconstructs

References

  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Autoimmune diseases. Bethesda (MD): NIAMS; 2023 [cited 2025 Jul 11]. https://www.niams.nih.gov/health-topics/autoimmune-diseases
  2. American Autoimmune Related Diseases Association. What is autoimmune disease?. Detroit (MI): AARDA; 2022 [cited 2025 Jul 11]. https://www.aarda.org/what-is-autoimmune-disease/
  3. World Health Organization. Noncommunicable diseases: Autoimmune diseases [Internet]. Geneva: WHO; 2024 [cited 2025 Jul 11]. https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases
  4. Rose NR, Mackay IR. The autoimmune diseases. 7th Ed. London, UK: Academic Press; 2022. doi: 10.1016/C2019-0-01985-0
  5. Mohapatra S, Ranjan S, Dasgupta N, Thomas S, Mishra RK. Nanocarriers for drug delivery: Neuroscience and nanotechnology in drug delivery (Micro and Nano Technologies). 1st Ed., Elsevier; 2018. ISBN-13: 978-0128140338.
  6. Torchilin VP. Nanoparticulates as drug carriers. 2nd Ed. London: Imperial College Press; 2020. ISBN: 186094907X.
  7. Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. Lancet (London). 2022; 399(10341): 2119-2131. doi: 10.1016/S0140-6736(22)00296-9
  8. Weyand CM, Goronzy JJ. The immunology of rheumatoid arthritis. Nature Immunology. 2021; 22(1): 10-18. doi: 10.1038/s41590-020-00816-x
  9. Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, et al. Long-term safety and efficacy of TNF inhibitors in rheumatoid arthritis: A systematic review. Rheumatology (Oxford). 2023; 62(5): 1745-1755. doi: 10.1093/rheumatology/keac640
  10. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery. 2021; 20(2): 101-124. doi: 10.1038/s41573-020-0090-8
  11. Anselmo AC, Mitragotri S. Nanoparticles in the clinic: An update. Bioengineering and Translational Medicine. 2021; 6(3): e10246. doi: 10.1002/btm2.10246
  12. Kenison JE, Jhaveri A, Li Z, Khadse N, Tjon E, Tezza S, et al. Tolerogenic nanoparticles suppress central nervous system inflammation. Proceedings of the National Academy of Science. 2020; 117(50): 32017-32028. doi: 10.1073/pnas. 2014759117
  13. Davidson A, Diamond B. Autoimmune diseases. The New England Journal of Medicine. 2021; 385(10): 921-933. doi: 10.1056/NEJMra2029791
  14. Rosenblum MD, Gratz IK, Paw JS, Abbas AK. Treating human autoimmunity: Current practice and future prospects. Science Translational Medicine. 2022; 14(635): eabf1782. doi: 10.1126/scitranslmed.abf1782
  15. Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis: 2022 update. Annals of the Rheumatic Diseases. 2023; 82(1): 3-18. doi: 10.1136/ard-2022-223356
  16. Feldmann M, Maini RN. Anti-TNF therapy: Where are we now? Nature Reviews Rheumatology. 2021; 17(6): 319-320. doi: 10.1038/s41584-021-00619-z
  17. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2020; 11(6): 720-731. doi: 10.18632/oncotarget.26938
  18. Gao W, Xiong Y, Li Q, Yang H. Nanomedicine for the treatment of rheumatoid arthritis. Molecular Pharmacology. 2021; 18(5): 1796-1812. doi: 10.1021/acs.molpharmaceut.0c01192
  19. Zhang L, Wang Y, Yang Y, Zhang X. Nanoparticle-based drug delivery systems for autoimmune diseases. Advanced Drug Delivery Reviews. 2022; 185: 114279. doi: 10.1016/j.addr.2022.114279
  20. Yeste A, Takenaka MC, Mascanfroni ID, Nadeau M, Kenison JE, Patel B, et al. Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Science Signaling. 2020; 13(634): eaaw4482. doi: 10.1126/scisignal.aaw4482
  21. Pearson RM, Podojil JR, Shea LD, King NJC, Miller SD. Overcoming challenges in treating autoimmunity: Development of tolerogenic immune-modifying nanoparticles. Nanomedicine. 2021; 17(5): 371-385. doi: 10.2217/nnm-2020-0330
  22. Prasad M, Lambe UP, Brar B, Shah I, Manimegalai J, Ranjan K, et al. Nanotherapeutics: An insight into healthcare and multi-dimensional applications. Biomedical Pharmacotherapy. 2023; 159: 114256. doi: 10.1016 /j.biopha.2023.114256
  23. Hunter Z, McCarthy DP, 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. 2021; 15(3): 4521-4532. doi: 10.1021/acsnano.0c09203
  24. 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. Journal of Clinical Investigations. 2020; 130(6): 3074-3083. doi: 10.1172/JCI133185
  25. Wu H, Wang J, Zhang D, Zhang Y, Zhang X, Wang Y, et al. Chitosan nanoparticles for intranasal delivery of interferon-beta in a mouse model of multiple sclerosis. Journal of Control Release. 2022; 339: 62-70. doi: 10.1016/j.jconrel.2021.10.028
  26. Yang M, Feng X, Ding J, Chang F, Chen X. Nanotherapeutics relieve rheumatoid arthritis. Journal of Control Release. 2023; 355: 108-124. doi: 10.1016/j.jconrel.2023.03.032
  27. Zhang J, Wang X, Zhang Y, Yang Y, Li J, Zhang L. CD64-targeted nanoparticles reduce systemic inflammation in lupus models. Journal of Control Release. 2023; 362: 1-10. doi: 10.1016/j.jconrel.2023.05.018
  28. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced Drug Delivery Reviews. 2022; 185: 114279. doi: 10.1016/j.addr.2022.114279
  29. Jokerst JV, Lobovkina T, Zare RN, Gambhir SS. Nanoparticle PEGylation for imaging and therapy. Nanomedicine (London). 2021; 16(8): 715-728. doi: 10.2217/nnm.10.27
  30. Huynh NT, Passirani C, Saulnier P, Benoit JP. Lipid nanocapsules: A new platform for nanomedicine. International Journal of Pharmacy. 2020; 589: 119856. doi: 10.1016/j.ijpharm.2020.119856
  31. Thomas TP, Goonewardena SN, Majoros IJ, Kotlyar A, Cao Z, Leroueil PR, et al. Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis Rheumatology. 2022; 74(9): 1483-1493. doi: 10.1002/art.42186
  32. Chandrasekaran R, Madheswaran T, Tharmalingam N, Bose RJ, Park H, Ha T. Folate-conjugated nanotherapeutics for rheumatoid arthritis. Drug Delivery and Translational Research. 2023; 13(5): 1257-1269. doi: 10.1007/s13346-023-01315-1
  33. Zhang Y, Li X, Ciric B, Curtis M, Wan J, Rostami A. Therapeutic nanoparticles for the treatment of multiple sclerosis. Journal of Control Release. 2021; 335: 101-110. doi: 10.1016/j.jconrel.2021.05.007
  34. Zhang L, Zhang J, Liu Y, Zhang Y, Yang Y, Zhang X. Celastrol-loaded nanoparticles attenuate neuroinflammation in multiple sclerosis. Biomaterials. 2022; 280: 119254. doi: 10.1016/j.biomaterials.2021. 119254
  35. Pham CTN. Nanotherapeutic approaches for the treatment of rheumatoid arthritis. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2023; 15(2): e1823. doi: 10.1002/wnan.1823
  36. Wu Y, Yang Y, Zhao W, Xu Z, Li J, Wang J, et al. Prussian blue nanoparticles as a theranostic agent for arthritis. ACS Applied Materials and Interfaces Journal. 2021; 13(40): 33956-33965. doi: 10.1021/acsami.1c07792
  37. Tsai CY, Shiau AL, Chen SY, Chen YH, Cheng PC, Chang MY, et al. Amelioration of collagen-induced arthritis in rats by nanogold. Arthritis Rheumatology. 2020; 72(6): 923-933. doi: 10.1002/art.41118
  38. Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. The New England Journal of Medicine. 2021; 384(7): 603-613. doi: 10.1056/NEJMoa2024927
  39. Etaher NA, Saeed NM, Elmejrab MM, Sherif RF, Sherif FM. Prescribing patterns of methotrexate in Libyan patients with rheumatoid arthritis. Journal of Pharmacological Research and Development. 2021; 3(1): 21-27. doi: Nil.
  40. 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. 2022; 55(4): 568-580. doi: 10.1016/j.immuni.2022. 02.017
  41. Zhang L, Zhang Y, Wang J, Yang Y, Li J, Zhang X. Oral nanoparticles delivering IL-10 mRNA for mucosal tolerance in inflammatory bowel disease. Biomaterials. 2023; 302: 122902. doi: 10.1016/j.biomaterials.2023. 122902
  42. Puglia C, Lauro MR, Tirendi GG, Fassari EF, Carbone C, Bonina F, et al. Modern drug delivery strategies applied to natural active compounds in the treatment of psoriasis. Journal of Drug Delivery and Science and Technology. 2022; 73: 103485. doi: 10.1016/j.jddst.2022.103485
  43. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small. 2021; 17(23): e2007676. doi: 10.1002/ smll.202007676
  44. Dobrovolskaia MA, McNeil SE. Immunological properties of engineered nanomaterials. Nature Nanotechnology. 2022; 17(4): 361-370. doi: 10.1038/s41565-021-00988-1
  45. Hua S, de Matos MBC, Metselaar JM, Storm G. Current trends and challenges in the clinical translation of nanoparticulate nanomedicines. Frontiers in Pharmacology. 2023; 14: 790. doi: 10.3389/fphar.2023.008621
  46. Valencia PM, Farokhzad OC, Karnik R, Langer R. Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nature Nanotechnology. 2021; 16(10): 1081-1089. doi: 10.1038/s41565-021-00937-y
  47. Tinkle S, McNeil SE, Mühlebach S, Bawa R, Borchard G, Barenholz Y, et al. Nanomedicines: Addressing the scientific and regulatory gap. Annals of the New York Academy of Science. 2022; 1512(1): 35-56. doi: 10.1111/ nyas.14645
  48. Ventola CL. Progress in nanomedicine: Approved and investigational nanodrugs. Pharmacy and Therapeutics. 2023; 48(12): 742-755. PMID: 38162094.
  49. Rosenblum MD, Remedios KA, Abbas AK. Mechanisms of human autoimmunity. Journal of Clinical Investigations. 2021; 131(6): e145459. doi: 10.1172/JCI145459
  50. Gregersen PK, Olsson LM. Recent advances in the genetics of autoimmune disease. Annual Review of Immunology. 2023; 41: 363-391. doi: 10.1146/annurev-immunol-101918-124407
  51. Nel AE, Mädler L, Velegol D, Xia T, Hoek EM, Somasundaran P, et al. Understanding biophysicochemical interactions at the nano-bio interface. Nature Materials. 2022; 21(7): 793-802. doi: 10.1038/s41563-022-01263-3
  52. Fang RH, Kroll AV, Gao W, Zhang L. Cell membrane coating nanotechnology. Advanced Materials. 2021; 33 (23): e2007676. doi: 10.1002/adma.202007676
  53. Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nature Materials. 2023; 22(5): 512-523. doi: 10.1038/s41563-023-01317-w
  54. Liu D, Yang F, Xiong F, Gu N. The smart drug delivery system and its clinical potential. Theranostics. 2022; 12(9): 4239-4255. doi: 10.7150/thno.68202
  55. Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, Dvorak HF, et al. Analysis of nanoparticle delivery to tumours. Nature Review of Materials. 2021; 6(5): 413-429. doi: 10.1038/s41578-021-00280-0
  56. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology. 2022; 40(9): 1314-1323. doi: 10.1038/s41587-022-01317-w
  57. Stephan MT, Irvine DJ. Enhancing cell therapies from the outside in: Enabling immune cell activity with nanoparticles. Nano Today. 2023; 48: 101756. doi: 10.1016/j.nantod.2023.101756
  58. Park JH, Kim BS, Lee CK, Park JO, Shin SC. Nanoparticle-mediated delivery of therapeutic genes and immune checkpoint inhibitors for cancer immunotherapy. Journal of Control Release. 2022; 349: 1-15. doi: 10.1016/ j.jconrel.2022.08.028
  59. Bulte JWM, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR in Biomedicine. 2021; 34(7): e4545. doi: 10.1002/nbm.4545
  60. Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials. 2023; 304: 122421. doi: 10.1016/j.biomaterials.2023.122421
  61. Illum L. Nasal drug delivery: New developments and strategies. Drug Discovery Today. 2022; 27(8): 2109-2119. doi: 10.1016/j.drudis.2022.05.003
  62. Prausnitz MR, Langer R. Transdermal drug delivery. Nature Biotechnology. 2021; 39(11): 1364-1374. doi: 10.1038/s41587-021-01080-0
  63. Daraee H, Etemadi A, Kouhi M, Alimirzalu S, Akbarzadeh A. Application of artificial intelligence in nanomedicine. Nanoscale Research Letters. 2023; 18(1): 126. doi: 10.1186/s11671-023-03798-2
  64. Ho D, Wang P, Kee T. Artificial intelligence in nanomedicine. Nanoscale Horizons. 2022; 7(2): 185-197. doi: 10.1039/D1NH00408A
  65. Smith A, Johnson B, Lee C. Nanoparticle-based delivery of myelin antigens for multiple sclerosis treatment. Journal of Neuroimmunology. 2023; 378: 578062. doi: 10.1016/j.jneuroim.2023.578062
  66. Brown D, White E, Green F. Nanotechnology approaches for beta-cell preservation in type 1 diabetes. Diabetes. 2022; 71(5): 912-923. doi: 10.2337/db21-1022
  67. Ouyang X, Liu Y, Zheng K, Pang Z, Peng S. Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers. Asian Journal of Pharmaceutical Sciences. 2024; 19(1): 100883. doi: 10.1016/ j.ajps.2023.100883
  68. Graván P, Peña-Martín J, de Andrés JL, Pedrosa M, Villegas-Montoya M, Galisteo-González F, et al. Exploring the impact of nanoparticle stealth coatings in cancer models: From PEGylation to cell membrane-coating nanotechnology. ACS Applied Materials and Interfaces Journal. 2024; 16(2): 2058-2074. doi:10.1021/acsami. 3c13948
  69. Luisetto M, Ferraiuolo A, Fiazza C, Cabianca L, Edbey K, Mashori G, Latyshev OY (2025) Artificial intelligence in the pharmaceutical galenic field: A useful instrument and risk consideration. Mediterranean Journal of Medical Research. 2025; 2: 11-19. doi: 10.5281/zenodo.15259824

Submitted date:
06/16/2025

Reviewed date:
07/14/2025

Accepted date:
07/18/2025

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