Inflammation responsive tofacitinib loaded albumin nanomedicine for targeted synergistic therapy in ulcerative colitis

Bang Li; Xiaoyan Liu; Qi Long; Xiaoduan Zhuang; Yanfei Gao; Barkat Ali; Haoting Chen; Dongyang Zhang; Xinying Wang; Weisheng Guo

doi:10.1007/s12274-023-5743-6

Nano Research 2023, 16(7): 9873-9884 https://doi.org/10.1007/s12274-023-5743-6

Research Article | Issue | Published: 02 June 2023

Inflammation responsive tofacitinib loaded albumin nanomedicine for targeted synergistic therapy in ulcerative colitis

Show Author's Information Hide Author's Information Bang Li^{¹^,^§}, Xiaoyan Liu^{¹^,^§}, Qi Long^{²^,^§}, Xiaoduan Zhuang^¹, Yanfei Gao^¹, Barkat Ali^², Haoting Chen^², Dongyang Zhang^²(

), Xinying Wang^¹(

), Weisheng Guo^²(

)

1Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China

2Department of Minimally Invasive Interventional Radiology, the State Key Laboratory of Respiratory Disease, School of Biomedical Engineering & The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China

^§ Bang Li, Xiaoyan Liu, and Qi Long contributed equally to this work.

Keywords:

ulcerative colitis, targeted delivery, tofacitinib, mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1), reactive oxygen species (ROS)-responsive

Topics:

Drug delivery Medical problems Targeted drug delivery

Cite this article:

Li B, Liu X, Long Q, et al. Inflammation responsive tofacitinib loaded albumin nanomedicine for targeted synergistic therapy in ulcerative colitis. Nano Research, 2023, 16(7): 9873-9884. https://doi.org/10.1007/s12274-023-5743-6

Download citation

EndNote(RIS)

BibTeX

715

Views

Downloads

Citations

Crossref

WoS

Scopus

CSCD

Abstract Full text Electronic supplementary material About this article

Abstract

Patients with ulcerative colitis (UC) often loss responses over long term usage of conventional therapies. Tofacitinib, a pan-Janus kinases (JAK) inhibitor is approved for moderate to severe UC treatment, while dose-limiting systemic side effects including infections, cancers and lymphoma limit its popularity of clinical application. This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1 (anti-MAdCAM-1) antibody modified reactive oxygen species (ROS) responsive human serum albumin-based nanomedicine denoted as THM, to improve the therapeutic efficacy of tofacitinib for UC treatment. THM has the drug releasing properties in response to ROS stimulation. In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages. Meanwhile, the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing. In addition, in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon. Moreover, THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis. This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.

Full text

Abstract

Full text

Outline

Electronic supplementary material

About this article

Inflammation responsive tofacitinib loaded albumin nanomedicine for targeted synergistic therapy in ulcerative colitis

Show Author's information Hide Author's Information Bang Li^{¹^,^§}, Xiaoyan Liu^{¹^,^§}, Qi Long^{²^,^§}, Xiaoduan Zhuang^¹, Yanfei Gao^¹, Barkat Ali^², Haoting Chen^², Dongyang Zhang^²(

), Xinying Wang^¹(

), Weisheng Guo^²(

)

1Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China

^§ Bang Li, Xiaoyan Liu, and Qi Long contributed equally to this work.

Abstract

Keywords: ulcerative colitis, targeted delivery, tofacitinib, mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1), reactive oxygen species (ROS)-responsive

References(39)

[1]

Graham, D. B.; Xavier, R. J. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature 2020, 578, 527–539.

DOI Google Scholar

[2]

Pantavou, K.; Yiallourou, A. I.; Piovani, D.; Evripidou, D.; Danese, S.; Peyrin-Biroulet, L.; Bonovas, S.; Nikolopoulos, G. K. Efficacy and safety of biologic agents and tofacitinib in moderate-to-severe ulcerative colitis: A systematic overview of meta-analyses. United European Gastroenterol. J. 2019, 7, 1285–1303.

DOI Google Scholar

[3]

Singh, S.; Allegretti, J. R.; Siddique, S. M.; Terdiman, J. P. AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology 2020, 158, 1465–1496.e17.

DOI Google Scholar

[4]

Dulai, P. S.; Singh, S.; Casteele, N. V.; Meserve, J.; Winters, A.; Chablaney, S.; Aniwan, S.; Shashi, P.; Kochhar, G.; Weiss, A. et al. Development and validation of clinical scoring tool to predict outcomes of treatment with vedolizumab in patients with ulcerative colitis. Clin. Gastroenterol. Hepatol. 2020, 18, 2952–2961.e8.

DOI Google Scholar

[5]

Sandborn, W. J.; Su, C.; Panes, J. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2017, 377, 496–497.

DOI Google Scholar

[6]

Zhang, Y. Z.; Li, Y. Y. Inflammatory bowel disease: pathogenesis. World J. Gastroenterol. 2014, 20, 91-99.

DOI Google Scholar

[7]

Coskun, M.; Salem, M.; Pedersen, J.; Nielsen, O. H. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol. Res. 2013, 76, 1–8.

DOI Google Scholar

[8]

Soendergaard, C.; Bergenheim, F. H.; Bjerrum, J. T.; Nielsen, O. H. Targeting JAK-STAT signal transduction in IBD. Pharmacol. Ther. 2018, 192, 100–111.

DOI Google Scholar

[9]

Salas, A.; Hernandez-Rocha, C.; Duijvestein, M.; Faubion, W.; McGovern, D.; Vermeire, S.; Vetrano, S.; Casteele, N. V. JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 323–337.

DOI Google Scholar

[10]

Fernández-Clotet, A.; Castro-Poceiro, J.; Panés, J. Tofacitinib for the treatment of ulcerative colitis. Expert Rev. Clin. Immunol. 2018, 14, 881–892.

DOI Google Scholar

[11]

Yang, M.; Zhang, Y. J.; Ma, Y. N.; Yan, X. J.; Gong, L. Y.; Zhang, M. Z.; Zhang, B. J. Nanoparticle-based therapeutics of inflammatory bowel diseases: A narrative review of the current state and prospects. J. Bio-X Res. 2020, 3, 157–173.

DOI Google Scholar

[12]

Nunes, R.; Neves, J. D.; Sarmento, B. Nanoparticles for the regulation of intestinal inflammation: Opportunities and challenges. Nanomedicine 2019, 14, 2631–2644.

DOI Google Scholar

[13]

Pertuit, D.; Moulari, B.; Betz, T.; Nadaradjane, A.; Neumann, D.; Ismaïli, L.; Refouvelet, B.; Pellequer, Y.; Lamprecht, A. 5-amino salicylic acid bound nanoparticles for the therapy of inflammatory bowel disease. J. Control. Release 2007, 123, 211–218.

DOI Google Scholar

[14]

Makhlof, A.; Tozuka, Y.; Takeuchi, H. pH-Sensitive nanospheres for colon-specific drug delivery in experimentally induced colitis rat model. Eur. J. Pharm. Biopharm. 2009, 72, 1–8.

DOI Google Scholar

[15]

Xiao, B.; Laroui, H.; Ayyadurai, S.; Viennois, E.; Charania, M. A.; Zhang, Y. C.; Merlin, D. Mannosylated bioreducible nanoparticle-mediated macrophage-specific TNF-α RNA interference for IBD therapy. Biomaterials 2013, 34, 7471–7482.

DOI Google Scholar

[16]

Zhang, J. X.; Zhao, Y. G.; Hou, T. L.; Zeng, H. R.; Kalambhe, D.; Wang, B.; Shen, X. Y.; Huang, Y. Z. Macrophage-based nanotherapeutic strategies in ulcerative colitis. J. Control. Release 2020, 320, 363–380.

DOI Google Scholar

[17]

Zhang, S. F.; Langer, R.; Traverso, G. Nanoparticulate drug delivery systems targeting inflammation for treatment of inflammatory bowel disease. Nano Today 2017, 16, 82–96.

DOI Google Scholar

[18]

Gao, Y. F.; Xu, A. G.; Shen, Q.; Xie, Y.; Liu, S. L.; Wang, X. Y. Graphene oxide aggravated dextran sulfate sodium-induced colitis through intestinal epithelial cells autophagy dysfunction. J. Toxicol. Sci. 2021, 46, 43–55.

DOI Google Scholar

[19]

Zhang, D. Y.; Zheng, Y.; Zhang, H.; Sun, J. H.; Tan, C. P.; He, L.; Zhang, W.; Ji, L. N.; Mao, Z. W. Delivery of phosphorescent anticancer iridium(III) complexes by polydopamine nanoparticles for targeted combined photothermal-chemotherapy and thermal/photoacoustic/lifetime imaging. Adv. Sci. 2018, 5, 1800581.

DOI Google Scholar

[20]

Liu, L.; Hu, F. L.; Wang, H.; Wu, X. L.; Eltahan, A. S.; Stanford, S.; Bottini, N.; Xiao, H. H.; Bottini, M.; Guo, W. S. et al. Secreted protein acidic and rich in cysteine mediated biomimetic delivery of methotrexate by albumin-based nanomedicines for rheumatoid arthritis therapy. ACS Nano 2019, 13, 5036–5048.

DOI Google Scholar

[21]

Verstockt, B.; Vetrano, S.; Salas, A.; Nayeri, S.; Duijvestein, M.; Casteele, N. V. Sphingosine 1-phosphate modulation and immune cell trafficking in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 2022, 19, 351–366.

DOI Google Scholar

[22]

Briskin, M.; Winsor-Hines, D.; Shyjan, A.; Cochran, N.; Bloom, S.; Wilson, J.; McEvoy, L. M.; Butcher, E. C.; Kassam, N.; Mackay, C. R. et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am. J. Pathol. 1997, 151, 97–110.

Google Scholar

[23]

Arihiro, S.; Ohtani, H.; Suzuki, M.; Murata, M.; Ejima, C.; Oki, M.; Kinouchi, Y.; Fukushima, K.; Sasaki, I.; Nakamura, S.; Matsumoto, T.; Torii, A.; Toda, G.; Nagura, H. Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Pathol. Int. 2002, 52, 367–374.

DOI Google Scholar

[24]

Wu, Y. W.; Briley, K.; Tao, X. F. Nanoparticle-based imaging of inflammatory bowel disease. WIREs Nanomed. Nanobiotechnol. 2016, 8, 300–315.

DOI Google Scholar

[25]

Nakase, H.; Sato, N.; Mizuno, N.; Ikawa, Y. The influence of cytokines on the complex pathology of ulcerative colitis. Autoimmun. Rev. 2022, 21, 103017.

DOI Google Scholar

[26]

Su, X. D.; Yu, Y. P.; Zhong, Y.; Giannopoulou, E. G.; Hu, X. Y.; Liu, H.; Cross, J. R.; Rätsch, G.; Rice, C. M.; Ivashkiv, L. B. Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation. Nat. Immunol. 2015, 16, 838–849.

DOI Google Scholar

[27]

Zhen, Y.; Zhang, H. NLRP3 inflammasome and inflammatory bowel disease. Front. Immunol. 2019, 10, 276.

DOI

[28]

Neurath, M. F. Cytokines in inflammatory bowel disease. Nat. Rev. Immunol. 2014, 14, 329–342.

DOI Google Scholar

[29]

Sun, Y.; Sun, X. L.; Li, X.; Li, W.; Li, C. Y.; Zhou, Y. M.; Wang, L.; Dong, B. A versatile nanocomposite based on nanoceria for antibacterial enhancement and protection from aPDT-aggravated inflammation via modulation of macrophage polarization. Biomaterials 2021, 268, 120614.

DOI Google Scholar

[30]

Bai, J. X.; Wang, H. Y.; Chen, H.; Ge, G. R.; Wang, M.; Gao, A.; Tong, L. P.; Xu, Y. Z.; Yang, H. L.; Pan, G. Q. et al. Biomimetic osteogenic peptide with mussel adhesion and osteoimmunomodulatory functions to ameliorate interfacial osseointegration under chronic inflammation. Biomaterials 2020, 255, 120197.

DOI Google Scholar

[31]

He, W.; Kapate, N.; Shields IV, C. W.; Mitragotri, S. Drug delivery to macrophages: A review of targeting drugs and drug carriers to macrophages for inflammatory diseases. Adv. Drug Delivery Rev. 2020, 165–166, 15–40.

DOI Google Scholar

[32]

Perdiguero, E. G.; Klapproth, K.; Schulz, C.; Busch, K.; Azzoni, E.; Crozet, L.; Garner, H.; Trouillet, C.; De Bruijn, M. F.; Geissmann, F. et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 2015, 518, 547–551.

DOI Google Scholar

[33]

Watanabe, C.; Miura, S.; Hokari, R.; Teramoto, K.; Ogino, T.; Komoto, S.; Hara, Y.; Koseki, S.; Tsuzuki, Y.; Nagata, H. et al. Spatial heterogeneity of TNF-α-induced T cell migration to colonic mucosa is mediated by MAdCAM-1 and VCAM-1. Am. J. Physiol. -Gastrointest. Liver Physiol. 2002, 283, G1379–1387.

DOI Google Scholar

[34]

De Chaisemartin, L.; Goc, J.; Damotte, D.; Validire, P.; Magdeleinat, P.; Alifano, M.; Cremer, I.; Fridman, W. H.; Sautès-Fridman, C.; Dieu-Nosjean, M. C. Characterization of chemokines and adhesion molecules associated with T cell presence in tertiary lymphoid structures in human lung cancer. Cancer Res. 2011, 71, 6391–6399.

DOI Google Scholar

[35]

Hoffmann, M.; Schwertassek, U.; Seydel, A.; Weber, K.; Falk, W.; Hauschildt, S.; Lehmann, J. A refined and translationally relevant model of chronic DSS colitis in BALB/c mice. Lab. Anim. 2018, 52, 240–252.

DOI Google Scholar

[36]

Miles, A.; Liaskou, E.; Eksteen, B.; Lalor, P. F.; Adams, D. H. CCL25 and CCL28 promote α₄β₇-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow. Am. J. Physiol. -Gastrointest. Liver Physiol. 2008, 294, G1257–G1267.

DOI Google Scholar

[37]

Luettig, J.; Rosenthal, R.; Lee, I. F. M.; Krug, S. M.; Schulzke, J. D. The ginger component 6-shogaol prevents TNF-α-induced barrier loss via inhibition of PI3K/Akt and NF-κB signaling. Mol. Nutr. Food Res. 2016, 60, 2576–2586.

DOI Google Scholar

[38]

Berlin, C.; Berg, E. L.; Briskin, M. J.; Andrew, D. P.; Kilshaw, P. J.; Holzmann, B.; Weissman, I. L.; Hamann, A.; Butcher, E. C. α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 1993, 74, 185–195.

DOI Google Scholar

[39]

Gerlach, K.; Lechner, K.; Popp, V.; Offensperger, L.; Zundler, S.; Wiendl, M.; Becker, E.; Atreya, R.; Rath, T.; Neurath, M. F. et al. The JAK1/3 inhibitor to tofacitinib suppresses T cell homing and activation in chronic intestinal inflammation. J. Crohn's Colitis 2021, 15, 244–257.

DOI Google Scholar

Electronic supplementary material

File

12274_2023_5743_MOESM1_ESM.pdf (1.8 MB)

About this article

Publication history

Acknowledgements

Publication history

Received: 24 February 2023

Revised: 12 April 2023

Accepted: 14 April 2023

Published: 02 June 2023

Issue date: July 2023

Copyright

Acknowledgements

This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 31971302 and 82170532), the Natural Science Foundation of Guangdong Province of China (No. 2019A1515011597), the talent young scientist supporting program of China Association for Science and Technology, the Educational Commission of Guangdong Province of China key Project (No. 2020ZDZX2001), the joint grant between Guangzhou City and College (No. 202102010106), and Guangzhou Science and Technology Plan Project (No. 202201011509).