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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Medicine</journal-id><journal-title-group><journal-title xml:lang="en">Russian Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский медицинский журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0869-2106</issn><issn publication-format="electronic">2412-9100</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">680779</article-id><article-id pub-id-type="doi">10.17816/medjrf680779</article-id><article-id pub-id-type="edn">SBCIYG</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Научные обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">New targets and nanotheranostics in rheumatoid arthritis therapy: a review</article-title><trans-title-group xml:lang="ru"><trans-title>Новые мишени и нанотераностика в терапии ревматоидного артрита: литературный обзор</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-7450-9213</contrib-id><name-alternatives><name xml:lang="en"><surname>Sukhov</surname><given-names>Alexander A.</given-names></name><name xml:lang="ru"><surname>Сухов</surname><given-names>Александр Александрович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>a.suhov2003@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7047-1436</contrib-id><contrib-id contrib-id-type="spin">6320-7369</contrib-id><name-alternatives><name xml:lang="en"><surname>Chubarev</surname><given-names>Vladimir N.</given-names></name><name xml:lang="ru"><surname>Чубарев</surname><given-names>Владимир Николаевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), Professor</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор</p></bio><email>chubarev_v_n@staff.sechenov.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">The First Sechenov Moscow State Medical University</institution></aff><aff><institution xml:lang="ru">Первый Московский государственный медицинский университет имени И.М. Сеченова</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-12-07" publication-format="electronic"><day>07</day><month>12</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2025-12-31" publication-format="electronic"><day>31</day><month>12</month><year>2025</year></pub-date><volume>31</volume><issue>6</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>557</fpage><lpage>567</lpage><history><date date-type="received" iso-8601-date="2025-05-27"><day>27</day><month>05</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-07-01"><day>01</day><month>07</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Эко-Вектор</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2028-12-31"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref></license></permissions><self-uri xlink:href="https://medjrf.com/0869-2106/article/view/680779">https://medjrf.com/0869-2106/article/view/680779</self-uri><abstract xml:lang="en"><p>Rheumatoid arthritis is a severe chronic disease affecting the joints. It is associated with autoimmune imbalance and synovial inflammation. Despite the use of biological agents, a significant proportion of patients remain refractory to standard therapy. Consequently, the development of monoclonal antibodies against novel targets and the application of nanotheranostics to improve therapeutic efficacy and selectivity are of particular interest.</p> <p>This work aimed to critically review promising future therapeutic targets for monoclonal antibody–based treatments—interferon gamma, granulocyte–macrophage colony-stimulating factor, interleukin-7 receptor alpha, bile salt–stimulated lipase, and programmed cell death receptor-1—and to assess nanotheranostic approaches as a means to improve the treatment of rheumatoid arthritis.</p> <p>Novel monoclonal antibodies against inflammatory effectors, including emapalumab, otilimab, OSE-127, SOL-116, and peresolimab, may reduce rheumatoid arthritis progression and improve clinical outcomes. However, the nonspecific action of monoclonal antibodies toward autoreactive cells can cause severe adverse effects, necessitating more advanced approaches such as nanotheranostics. Current trends in the treatment of rheumatoid arthritis show increasing use of nanomaterials, particularly liposomes, delivered via monoclonal antibodies. The efficacy of such combinations may be improved by drugs encapsulated within liposomes, such as small noncoding RNAs capable of suppressing specific genes responsible for the development and persistence of rheumatoid arthritis. Targeted localization and internalization of liposomal contents can be activated by physical factors, including infrared radiation and ultrasound, or achieved through targeting receptors overexpressed on autoreactive cells that are capable of internalization into the cellular compartment.</p> <p>The integration of monoclonal antibodies with nanomaterials as drug carriers represents a promising direction in the treatment of rheumatoid arthritis, providing greater selectivity, safety, and potential for personalized treatment. Further development of these strategies may significantly improve outcomes and quality of life in patients resistant to standard therapies.</p></abstract><trans-abstract xml:lang="ru"><p>Ревматоидный артрит (РА) — тяжёлое хроническое заболевание, поражающее суставы. Оно связано с аутоиммунным дисбалансом и воспалением в синовии. Несмотря на использование биологических препаратов, значительная часть пациентов остаётся рефрактерной к стандартной терапии. В связи с этим особый интерес представляет разработка моноклональных антител с принципиально новыми мишенями, а также использование потенциала нанотераностики для повышения эффективности и селективности терапии.</p> <p>В обзоре критически рассмотрены перспективные мишени для будущего лечения на основе моноклональных антител: интерферон гамма; гранулоцитарно-макрофагальный колониестимулирующий фактор; интерлейкин 7 рецептора альфа; липаза, стимулированная солями желчных кислот; рецептор программируемой клеточной смерти 1 — и оценить нанотераностический подход в качестве метода улучшения лечения РА.</p> <p>Новые моноклональные антитела против эффекторов воспаления, включая эмапалумаб, отилимаб, OSE-127, SOL-116 и пересолимаб (peresolimab), могут уменьшить прогрессирование РА и увеличить шансы на благоприятный исход. Однако неспецифичность моноклональных антител по отношению к аутореактивным клеткам может привести к серьёзным побочным эффектам, и данное обстоятельство требует рассмотрения более совершенных подходов, таких как нанотераностика. Современные тенденции в терапии РА указывают на растущую частоту использования наноматериалов, в частности липосом, доставляемых с помощью моноклональных антител. Повышение эффективности такой комбинации могут обеспечить инкапсулированные в липосому препараты, такие как малые некодирующие молекулы рибонуклеиновой кислоты, которые способны подавлять специфические гены, ответственные за развитие и персистенцию РА. Целевая локализация и интернализация содержимого липосом может быть активирована физическими факторами, включая инфракрасное излучение и ультразвук, или же реализована нацеливанием на клеточные рецепторы, которые сверхэкспрессированы на аутореактивных клетках и способны к интернализации в клеточный компартмент.</p> <p>Интеграция моноклональных антител с наноматериалами в качестве носителей лекарственных препаратов представляет собой перспективное направление в терапии РА, обеспечивая более высокую селективность, безопасность и потенциал для персонализированного подхода. Дальнейшее развитие данных стратегий способно существенно улучшить прогноз и качество жизни пациентов, устойчивых к традиционным методам лечения.</p></trans-abstract><kwd-group xml:lang="en"><kwd>rheumatoid arthritis</kwd><kwd>interleukin</kwd><kwd>monoclonal antibodies</kwd><kwd>nanotheranostics</kwd><kwd>nanocarriers</kwd><kwd>immunoliposomes</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>ревматоидный артрит</kwd><kwd>интерлейкин</kwd><kwd>моноклональные антитела</kwd><kwd>нанотераностика</kwd><kwd>наноносители</kwd><kwd>иммунолипосомы</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Программа «Приоритет-2030»</institution></institution-wrap><institution-wrap><institution xml:lang="en">Priority 2030 Programme</institution></institution-wrap></funding-source></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV. Monoclonal antibody and intravenous immunoglobulin therapy for rheumatic diseases: rationale and mechanisms of action. Nat Clin Pract Rheumatol. 2007;3(5):262–272. doi: 10.1038/ncprheum0481</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Derksen VFAM, Huizinga TWJ, van der Woude D. The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Semin Immunopathol. 2017;39(4):437–446. doi: 10.1007/s00281-017-0627-z EDN: TOWNPA</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Radu AF, Bungau SG. Management of rheumatoid arthritis: an overview. Cells. 2021;10(11):2857. doi: 10.3390/cells10112857 EDN: VCIMCY</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Crayne CB, Albeituni S, Nichols KE, Cron RQ. The immunology of macrophage activation syndrome. Front Immunol. 2019;10:119. doi: 10.3389/fimmu.2019.00119 EDN: KTMKPP</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>De Benedetti F, Grom AA, Brogan PA, et al. Efficacy and safety of emapalumab in macrophage activation syndrome. Ann Rheum Dis. 2023;82(6):857–865. doi: 10.1136/ard-2022-223739 EDN: HDKEFP</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Bracaglia C, de Graaf K, Pires Marafon D, et al. Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2017;76(1):166–172. doi: 10.1136/annrheumdis-2015-209020 EDN: QCYBEH</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Fleischmann RM, van der Heijde D, Strand V, et al. Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2). Ann Rheum Dis. 2023;82(12):1516–1526. doi: 10.1136/ard-2023-224482 EDN: NYGWVK</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Fuentelsaz-Romero S, Cuervo A, Estrada-Capetillo L, et al. GM-CSF expression and macrophage polarization in joints of undifferentiated arthritis patients evolving to rheumatoid arthritis or psoriatic arthritis. Front Immunol. 2021;11:613975. doi: 10.3389/fimmu.2020.613975 EDN: LTSYAC</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Ponchel F, Churchman S, El-Jawhari JJ, et al. Interleukin-7: a potential factor supporting B-cell maturation in the rheumatoid arthritis synovium. Clin Exp Rheumatol. 2021;39(2):253–262. doi: 10.55563/clinexprheumatol/j6t7cj EDN: EXEYWW</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Zeng Z, Mao H, Lei Q, He Y. IL-7 in autoimmune diseases: mechanisms and therapeutic potential. Front Immunol. 2025;16:1545760. doi: 10.3389/fimmu.2025.1545760</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Sugamura K, Asao H, Kondo M, et al. The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol. 1996;14:179–205. doi: 10.1146/annurev.immunol.14.1.179</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Poirier N, Baccelli I, Belarif L, et al. First-in-human study in healthy subjects with the noncytotoxic monoclonal antibody OSE-127, a strict antagonist of IL-7Rα. J Immunol. 2023;210(6):753–763. doi: 10.4049/jimmunol.2200635 EDN: DBCPPB</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Lindquist S, Wang Y, Andersson EL, et al. Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders. PLoS One. 2023;18(8):e0289980. doi: 10.1371/journal.pone.0289980 EDN: XYNKSW</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Franck-Larsson K, Lindquist S, Wennerholm A, et al. A first-in-human clinical trial evaluating the safety and pharmacokinetics of SOL-116, a novel humanized monoclonal antibody targeting bile salt-stimulated lipase for the treatment of RA [abstract]. Arthritis Rheumatol. 2024;76(Suppl 9).</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8(3):239–245. doi: 10.1038/ni1443</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Cappelli LC, Gutierrez AK, Bingham CO 3rd, Shah AA. Rheumatic and musculoskeletal immune-related adverse events due to immune checkpoint inhibitors: a systematic review of the literature. Arthritis Care Res (Hoboken). 2017;69(11):1751–1763. doi: 10.1002/acr.23177</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Raptopoulou AP, Bertsias G, Makrygiannakis D, et al. The programmed death 1/programmed death ligand 1 inhibitory pathway is up-regulated in rheumatoid synovium and regulates peripheral T cell responses in human and murine arthritis. Arthritis Rheum. 2010;62(7):1870–1880. doi: 10.1002/art.27500</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Li S, Liao W, Chen M, et al. Expression of programmed death-1 (PD-1) on CD4+ and CD8+ T cells in rheumatoid arthritis. Inflammation. 2014;37(1):116–121. doi: 10.1007/s10753-013-9718-8 EDN: NRJJAZ</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Rao DA, Gurish MF, Marshall JL, et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature. 2017;542(7639):110–114. doi: 10.1038/nature20810</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11(2):141–151. doi: 10.1016/s1074-7613(00)80089-8</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Zhang S, Wang L, Li M, et al. The PD-1/PD-L pathway in rheumatic diseases. J Formos Med Assoc. 2021;120(1 Pt 1):48–59. doi: 10.1016/j.jfma.2020.04.004</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Cappelli LC, Gutierrez AK, Baer AN, et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis. 2017;76(1):43–50. doi: 10.1136/annrheumdis-2016-209595 EDN: YWCNCV</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Calabrese C, Kirchner E, Kontzias A, et al. Rheumatic immune-related adverse events of checkpoint therapy for cancer: case series of a new nosological entity. RMD Open. 2017;3(1):e000412. doi: 10.1136/rmdopen-2016-000412</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Belkhir R, Burel SL, Dunogeant L, et al. Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment. Ann Rheum Dis. 2017;76(10):1747–1750. doi: 10.1136/annrheumdis-2017-211216</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Tuttle J, Drescher E, Simón-Campos JA, et al. A phase 2 Trial of Peresolimab for adults with rheumatoid arthritis. N Engl J Med. 2023;388(20):1853–1862. doi: 10.1056/NEJMoa2209856 EDN: KZIEGN</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Tanner MR, Hu X, Huq R, et al. KCa1.1 inhibition attenuates fibroblast-like synoviocyte invasiveness and ameliorates disease in rat models of rheumatoid arthritis. Arthritis Rheumatol. 2015;67(1):96–106. doi: 10.1002/art.38883</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Ong ST, Bajaj S, Tanner MR, et al. Modulation of lymphocyte potassium channel KV1.3 by membrane-penetrating, joint-targeting immunomodulatory plant defensin. ACS Pharmacol Transl Sci. 2020;3(4):720–736. doi: 10.1021/acsptsci.0c00035 EDN: LEXYAO</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>More NE, Mandlik R, Zine S, et al. Exploring the therapeutic opportunities of potassium channels for the treatment of rheumatoid arthritis. Front Pharmacol. 2024;15:1286069. doi: 10.3389/fphar.2024.1286069 EDN: ANZCNM</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Kwon OC, Park MC, Kim YG. Interleukin-32 as a biomarker in rheumatic diseases: A narrative review. Front Immunol. 2023;14:1140373. doi: 10.3389/fimmu.2023.1140373 EDN: PVKVII</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Kwon OC, Kim S, Hong S, et al. Role of IL-32 gamma on bone metabolism in autoimmune arthritis. Immune Netw. 2018;18(3):e20. doi: 10.4110/in.2018.18.e20</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Madav Y, Barve K, Prabhakar B. Current trends in theranostics for rheumatoid arthritis. Eur J Pharm Sci. 2020;145:105240. doi: 10.1016/j.ejps.2020.105240 EDN: INKPJY</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Qamar N, Arif A, Bhatti A, John P. Nanomedicine: an emerging era of theranostics and therapeutics for rheumatoid arthritis. Rheumatology (Oxford). 2019;58(10):1715–1721. doi: 10.1093/rheumatology/kez286</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Feng X, Chen Y. Drug delivery targets and systems for targeted treatment of rheumatoid arthritis. J Drug Target. 2018;26(10):845–857. doi: 10.1080/1061186X.2018.1433680 EDN: ETDTFN</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Pirmardvand Chegini S, Varshosaz J, Taymouri S. Recent approaches for targeted drug delivery in rheumatoid arthritis diagnosis and treatment. Artif Cells Nanomed Biotechnol. 2018;46(sup2):502–514. doi: 10.1080/21691401.2018.1460373</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Koushki K, Keshavarz Shahbaz S, Keshavarz M, et al. Gold nanoparticles: multifaceted roles in the management of autoimmune disorders. Biomolecules. 2021;11(9):1289. doi: 10.3390/biom11091289 EDN: HJXOVV</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Zeng L, Geng H, Gu W, et al. Au nanoparticles attenuate RANKL-induced osteoclastogenesis by suppressing pre-osteoclast fusion. J Nanosci Nanotechnol. 2019;19(4):2166–2173. doi: 10.1166/jnn.2019.15764</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Lee H, Lee MY, Bhang SH, et al. Hyaluronate-gold nanoparticle/tocilizumab complex for the treatment of rheumatoid arthritis. ACS Nano. 2014;8(5):4790–4798. doi: 10.1021/nn500685h</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Zhao P, Wang Y, Wu A, et al. Roles of albumin-binding proteins in cancer progression and biomimetic targeted drug delivery. Chembiochem. 2018;19(17):1796–1805. doi: 10.1002/cbic.201800201</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Zhong J, Zhang Q, Zhang Z, et al. Albumin mediated reactive oxygen species scavenging and targeted delivery of methotrexate for rheumatoid arthritis therapy. Nano Research. 2022;15(1):153–161. doi: 10.1007/s12274-021-3449-1</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Zheng X, Yu X, Wang C, et al. Targeted co-delivery biomimetic nanoparticles reverse macrophage polarization for enhanced rheumatoid arthritis therapy. Drug Deliv. 2022;29(1):1025–1037. doi: 10.1080/10717544.2022.2057616 EDN: JIOZOR</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Liu M, Huang Y, Hu L, et al. Selective delivery of interleukine-1 receptor antagonist to inflamed joint by albumin fusion. BMC Biotechnol. 2012;12:68. doi: 10.1186/1472-6750-12-68 EDN: ICMAUB</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Martinho N, Florindo H, Silva L, et al. Molecular modeling to study dendrimers for biomedical applications. Molecules. 2014;19(12):20424–20467. doi: 10.3390/molecules191220424 EDN: USQJVF</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Wang Q, Sun X. Recent advances in nanomedicines for the treatment of rheumatoid arthritis. Biomater Sci. 2017;5(8):1407–1420. doi: 10.1039/c7bm00254h EDN: YGEPCI</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Oliveira IM, Gonçalves C, Oliveira EP, et al. PAMAM dendrimers functionalised with an anti-TNF α antibody and chondroitin sulphate for treatment of rheumatoid arthritis. Mater Sci Eng C Mater Biol Appl. 2021;121:111845. doi: 10.1016/j.msec.2020.111845 EDN: YSHHQU</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Hajebi S, Rabiee N, Bagherzadeh M, et al. Stimulus-responsive polymeric nanogels as smart drug delivery systems. Acta Biomater. 2019;92:1–18. doi: 10.1016/j.actbio.2019.05.018 EDN: WZDFWP</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Preman NK, Barki RR, Vijayan A, et al. Recent developments in stimuli-responsive polymer nanogels for drug delivery and diagnostics: A review. Eur J Pharm Biopharm. 2020;157:121–153. doi: 10.1016/j.ejpb.2020.10.009 EDN: INJYAN</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Mohammad Faizal NDF, Ramli NA, Mat Rani NNI, et al. Leveraging immunoliposomes as nanocarriers against SARS-CoV-2 and its emerging variants. Asian J Pharm Sci. 2023;18(6):100855. doi: 10.1016/j.ajps.2023.100855 EDN: JRZMZF</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Hama S, Sakai M, Itakura S, et al. Rapid modification of antibodies on the surface of liposomes composed of high-affinity protein A-conjugated phospholipid for selective drug delivery. Biochem Biophys Rep. 2021;27:101067. doi: 10.1016/j.bbrep.2021.101067 EDN: OQGGYL</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Charbe NB, Amnerkar ND, Ramesh B, et al. Small interfering RNA for cancer treatment: overcoming hurdles in delivery. Acta Pharm Sin B. 2020;10(11):2075–2109. doi: 10.1016/j.apsb.2020.10.005 EDN: YXQCNE</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Gargano G, Oliva F, Oliviero A, Maffulli N. Small interfering RNAs in the management of human rheumatoid arthritis. Br Med Bull. 2022;142(1):34–43. doi: 10.1093/bmb/ldac012 EDN: QHXVMX</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Guzmán-Guzmán IP, Ramírez-Vélez CI, Falfán-Valencia R, et al. PADI2 polymorphisms are significantly associated with rheumatoid arthritis, autoantibodies serologic status and joint damage in women from Southern Mexico. Front Immunol. 2021;12:718246. doi: 10.3389/fimmu.2021.718246 EDN: OXLQAM</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Curran AM, Naik P, Giles JT, Darrah E. PAD enzymes in rheumatoid arthritis: pathogenic effectors and autoimmune targets. Nat Rev Rheumatol. 2020;16(6):301–315. doi: 10.1038/s41584-020-0409-1 EDN: RTRDTL</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Damgaard D, Senolt L, Nielsen CH. Increased levels of peptidylarginine deiminase 2 in synovial fluid from anti-CCP-positive rheumatoid arthritis patients: Association with disease activity and inflammatory markers. Rheumatology (Oxford). 2016;55(5):918–927. doi: 10.1093/rheumatology/kev440</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Damgaard D, Senolt L, Nielsen MF, et al. Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen. Arthritis Res Ther. 2014;16(6):498. doi: 10.1186/s13075-014-0498-9 EDN: OQCHLR</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Foulquier C, Sebbag M, Clavel C, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. 2007;56(11):3541–3553. doi: 10.1002/art.22983</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Li P, Li M, Lindberg MR, et al. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010;207(9):1853–1862. doi: 10.1084/jem.20100239</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Hocking AM, Buckner JH. Genetic basis of defects in immune tolerance underlying the development of autoimmunity. Front Immunol. 2022;13:972121. doi: 10.3389/fimmu.2022.972121 EDN: VGFPMU</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Zhao G, Liu A, Zhang Y, et al. Nanoparticle-delivered siRNA targeting Bruton's tyrosine kinase for rheumatoid arthritis therapy. Biomater Sci. 2019;7(11):4698–4707. doi: 10.1039/c9bm01025d</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Lohchania B, Christopher AC, Arjunan P, et al. Diosgenin enhances liposome-enabled nucleic acid delivery and CRISPR/Cas9-mediated gene editing by modulating endocytic pathways. Front Bioeng Biotechnol. 2023;10:1031049. doi: 10.3389/fbioe.2022.1031049 EDN: SCZTXN</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Sukocheva OA, Liu J, Neganova ME, et al. Perspectives of using microRNA-loaded nanocarriers for epigenetic reprogramming of drug resistant colorectal cancers. Semin Cancer Biol. 2022;86(Pt 2):358–375. doi: 10.1016/j.semcancer.2022.05.012 EDN: CPVMDS</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Wiraja C, Mathiyazhakan M, Movahedi F, et al. Near-infrared light-sensitive liposomes for enhanced plasmid DNA transfection. Bioeng Transl Med. 2016;1(3):357–364. doi: 10.1002/btm2.10020 EDN: XRQAOD</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Li X, Yang C, Tao Y, et al. Near-infrared light-triggered thermosensitive liposomes modified with membrane peptides for the local chemo/photothermal therapy of melanoma. Onco Targets Ther. 2021;14:1317–1329. doi: 10.2147/OTT.S287272 EDN: OJNEUA</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Schroeder A, Avnir Y, Weisman S, et al. Controlling liposomal drug release with low frequency ultrasound: mechanism and feasibility. Langmuir. 2007;23(7):4019–4025. doi: 10.1021/la0631668 EDN: LQKTAN</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Campbell J, Lowe D, Sleeman MA. Developing the next generation of monoclonal antibodies for the treatment of rheumatoid arthritis. Br J Pharmacol. 2011;162(7):1470–1484. doi: 10.1111/j.1476-5381.2010.01183.x</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Fukui R, Murakami Y, Miyake K. New application of anti-TLR monoclonal antibodies: detection, inhibition and protection. Inflamm Regen. 2018;38:11. doi: 10.1186/s41232-018-0068-7 EDN: NBOZMU</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Thwaites R, Chamberlain G, Sacre S. Emerging role of endosomal Toll-like receptors in rheumatoid arthritis. Front Immunol. 2014;5:1. doi: 10.3389/fimmu.2014.00001 EDN: URDVFD</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Liu J, Wang X, Wang S, Liu F. Therapeutic potential of non-coding RNAs and TLR signalling pathways in rheumatoid arthritis. Curr Pharm Biotechnol. 2021;22(11):1490–1500. doi: 10.2174/1389201021666201001142829 EDN: IAIWIZ</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Arleevskaya MI, Larionova RV, Brooks WH, et al. Toll-like receptors, infections, and rheumatoid arthritis. Clin Rev Allergy Immunol. 2020;58(2):172–181. doi: 10.1007/s12016-019-08742-z EDN: ZYWHMJ</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Santos-Sierra S. Targeting Toll-like receptor (TLR) pathways in inflammatory arthritis: two better than one? Biomolecules. 2021;11(9):1291. doi: 10.3390/biom11091291 EDN: UQFZQW</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Kim KW, Cho ML, Lee SH, et al. Human rheumatoid synovial fibroblasts promote osteoclastogenic activity by activating RANKL via TLR-2 and TLR-4 activation. Immunol Lett. 2007;110(1):54–64. doi: 10.1016/j.imlet.2007.03.004</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Clanchy FIL, Borghese F, Bystrom J, et al. TLR expression profiles are a function of disease status in rheumatoid arthritis and experimental arthritis. J Autoimmun. 2021;118:102597. doi: 10.1016/j.jaut.2021.102597 EDN: TFFSGQ</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Hu F, Li Y, Zheng L, et al. Toll-like receptors expressed by synovial fibroblasts perpetuate Th1 and th17 cell responses in rheumatoid arthritis. PLoS One. 2014;9(6):e100266. doi: 10.1371/journal.pone.0100266</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Iwahashi M, Yamamura M, Aita T, et al. Expression of Toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis. Arthritis Rheum. 2004;50(5):1457–1467. doi: 10.1002/art.20219</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Murakami Y, Fukui R, Tanaka R, et al. Anti-TLR7 antibody protects against lupus nephritis in NZBWF1 mice by targeting B cells and patrolling monocytes. Front Immunol. 2021;12:777197. doi: 10.3389/fimmu.2021.777197 EDN: CNKLTA</mixed-citation></ref></ref-list></back></article>
