Citation: Mengjie Wang, Shilin Li, Manman Ning, Yueguang Xue, Ke Xu, Xinran Wang, Shasha Jiang, Yongfu Ma, Ying Liu. Surface modification of iron oxide nanoparticles for enhanced therapeutic efficacy in inflammatory bowel disease[J]. Chinese Chemical Letters, ;2026, 37(10): 112139. doi: 10.1016/j.cclet.2025.112139 shu

Surface modification of iron oxide nanoparticles for enhanced therapeutic efficacy in inflammatory bowel disease

Mengjie Wang ^{a, b, 1} ,
Shilin Li ^{a, c, 1} ,
Manman Ning ^{a, 1} ,
Yueguang Xue ^{a, d} ,
Ke Xu ^{a, c} ,
Xinran Wang ^e ,
Shasha Jiang ^{f, *,} ,
Yongfu Ma ^g, ,
Ying Liu ^{a, *,}

a.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China
b.
Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310006, China
c.
University of Chinese Academy of Sciences, Beijing 100049, China
d.
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou 511442, China
e.
The Hong Kong University of Science and Technology, Hong Kong 999077, China
f.
The 990th Hospital of the Jointservice Support Force of the PLA, Zhumadian 463000, China
g.
Department of Thoracic Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China

jiangshasha1114@163.com

yongfuabc@sina.com

liuy@nanoctr.cn

Received Date: 28 June 2025
Revised Date: 18 November 2025
Accepted Date: 20 November 2025
Available Online: 20 November 2025

Figures(4)

Inflammatory bowel disease (IBD) is a chronic condition that severely affects the gastrointestinal tract. Current treatments often have limited efficacy and significant side effects. Iron oxide nanoparticles (Fe₂O₃ NPs) have emerged as promising candidates for IBD therapy due to their biocompatibility and stability. This study investigates how different surface modifications influence the therapeutic efficacy of Fe₂O₃ NPs in IBD management. We developed four different types of modified Fe₂O₃ NPs, including unmodified γ-Fe₂O₃ NPs, amine-functionalized Fe₂O₃ NPs (APTS-Fe₂O₃ NPs), poly-L-lysine-coated Fe₂O₃ NPs (PLL-Fe₂O₃ NPs), and dimercaptosuccinic acid-coated Fe₂O₃ NPs (DMSA-Fe₂O₃ NPs). Our results demonstrate that all types of Fe₂O₃ NPs can adsorb proteins to form the protein corona. However, the composition of the protein corona varies, leading to different therapeutic effects of the NPs on IBD. Among them, APTS-Fe₂O₃ NPs showed reduced therapeutic efficacy compared to the other surface-modified NPs. This was attributed to their adsorption of higher levels of protective and translocation-related proteins, as well as enhanced permeability across intestinal epithelial cells. These findings underscore the importance of carefully tailoring nanoparticle surface properties. Overall, this study highlights the significance of understanding nanoparticle-protein interactions in designing more effective nanoparticle-based therapies for IBD.
- Inflammatory bowel disease,
- Iron oxide nanoparticle,
- Protein corona,
- Surface modification,
- Multicellular model
1. [1]
  A.N. Ananthakrishnan, Nat. Rev. Gastroenterol. Hepatol. 12 (2015) 205–217. doi: 10.1038/nrgastro.2015.34
2. [2]
  Y.Z. Zhang, Y.Y. Li, World J. Gastroenterol. 20 (2014) 91–99. doi: 10.3748/wjg.v20.i1.91
3. [3]
  S.C. Ng, H.Y. Shi, N. Hamidi, et al., Lancet 390 (2017) 2769–2778. doi: 10.1016/S0140-6736(17)32448-0
4. [4]
  C.N. Bernstein, F. Shanahan, Gut 57 (2008) 1185–1191. doi: 10.1136/gut.2007.122143
5. [5]
  N.A. Molodecky, G.G. Kaplan, Gastroenterol. Hepatol. 6 (2010) 339–346.
6. [6]
  K.R. Nielsen, S.N. Lophaven, J. Midjord, et al., Inflamm. Bowel Dis. 31 (2025) 952–962. doi: 10.1093/ibd/izae120
7. [7]
  S. Danese, C. Fiocchi, N. Engl. J. Med. 365 (2011) 1713–1725. doi: 10.1056/NEJMra1102942
8. [8]
  P. Rutgeerts, W.J. Sandborn, B.G. Feagan, et al., N. Engl. J. Med. 353 (2005) 2462–2476. doi: 10.1056/NEJMoa050516
9. [9]
  W.J. Sandborn, B.G. Feagan, P. Rutgeerts, et al., N. Engl. J. Med. 369 (2013) 711–721. doi: 10.1056/NEJMoa1215739
10. [10]
  D.C. Baumgart, W.J. Sandborn, Lancet 380 (2012) 1590–1605. doi: 10.1016/S0140-6736(12)60026-9
11. [11]
  B. Huang, T. Yin, S. Fu, et al., Proc. Natl. Acad. Sci. U. S. A. 121 (2024) e2320482121. doi: 10.1073/pnas.2320482121
12. [12]
  C. Yang, K. Sharma, R.J. Mow, et al., Cell. Mol. Gastroenterol. Hepatol. 18 (2024) 101333. doi: 10.1016/j.jcmgh.2024.03.005
13. [13]
  W. Fu, L. Xu, Z. Chen, et al., J. Control. Release 363 (2023) 149–179. doi: 10.1016/j.jconrel.2023.09.033
14. [14]
  L. Wang, M. Yu, H. Yang, J. Inflamm. Res. 14 (2021) 1701–1716. doi: 10.2147/jir.s304101
15. [15]
  P.G. Balaji, L.S. Bhimrao, A.K. Yadav, Mol. Neurobiol. 62 (2024) 184–220.
16. [16]
  A.N. Vaneev, O.A. Kost, N.L. Eremeev, et al., Biomedicines 9 (2021) 396. doi: 10.3390/biomedicines9040396
17. [17]
  E. Tüzün, Chapter 15-nanotechnology-based management of neurological autoimmune diseases, in: Y. Gürsoy-Özdemir, S. Bozdağ-Pehlivan, E. Sekerdag (Eds.), Nanotechnology Methods for Neurological Diseases and Brain Tumors, Academic Press, 2017, pp. 279–290.
18. [18]
  M. Liu, Y. Wang, Y. Li, et al., MedComm Biomater. Appl. 4 (2025) e70012.
19. [19]
  T. Pan, D. Zhang, G. You, et al., Chin. Chem. Lett. 36 (2025) 109857. doi: 10.1016/j.cclet.2024.109857
20. [20]
  H. Hu, L. Yu, Z. Ding, et al., Chin. Chem. Lett. 34 (2023) 108592. doi: 10.1016/j.cclet.2023.108592
21. [21]
  T. Chen, W. Meng, Y. Li, et al., Nano Lett. 24 (2024) 7321–7331. doi: 10.1021/acs.nanolett.4c01143
22. [22]
  Y. Dai, Y. Guo, W. Tang, et al., J. Nanobiotechnology 22 (2024) 252. doi: 10.1186/s12951-024-02501-9
23. [23]
  E. Alphandéry, Drug Discov. Today 25 (2020) 141–149. doi: 10.1016/j.drudis.2019.09.020
24. [24]
  Y. Ma, H. Wu, M. Jia, et al., J. Nanopart. Res. 26 (2024) 250. doi: 10.1007/s11051-024-06169-y
25. [25]
  R. Wei, Y. Xu, M. Xue, J. Mater. Chem. B 9 (2021) 1965–1979. doi: 10.1039/d0tb02858d
26. [26]
  K. Xu, Y. Cui, B. Guan, et al., Nanoscale 16 (2024) 7786–7824. doi: 10.1039/d4nr00155a
27. [27]
  A. Abdelkawi, A. Slim, Z. Zinoune, Y. Pathak, Coatings 13 (2023) 1660. doi: 10.3390/coatings13091660
28. [28]
  S.Z. Alshawwa, A.A. Kassem, R.M. Farid, et al., Pharmaceutics 14 (2022) 883. doi: 10.3390/pharmaceutics14040883
29. [29]
  X.Y. You, H.Y. Zhang, X. Han, et al., Front. Pharmacol. 12 (2021) 659716. doi: 10.3389/fphar.2021.659716
30. [30]
  K.N. Dileepan, V.V. Raveendran, R. Sharma, et al., Front. Med. 10 (2023) 1213320. doi: 10.3389/fmed.2023.1213320
31. [31]
  T. Leech, M. Peiris, J. Gastroenterol. 59 (2024) 165–178. doi: 10.1007/s00535-023-02065-9
32. [32]
  D. Yazici, I. Ogulur, Y. Pat, et al., Semin. Immunol. 70 (2023) 101846. doi: 10.1016/j.smim.2023.101846
33. [33]
  T.A. Suárez Vázquez, N. López López, M.C. Salinas Carmona, Front. Immunol. 15 (2024) 1360296. doi: 10.3389/fimmu.2024.1360296
34. [34]
  D.Elieh Ali Komi, K. Grauwet, Clin. Rev. Allergy Immunol. 54 (2018) 432–445. doi: 10.1007/s12016-017-8646-z
35. [35]
  R. Berni Canani, M. Caminati, L. Carucci, I. Eguiluz-Gracia, Allergy 79 (2024) 1485–1500. doi: 10.1111/all.16092
36. [36]
  B.Y. De Winter, R.M. van den Wijngaard, W.J. de Jonge, Biochim. Biophys. Acta 1822 (2012) 66–73. doi: 10.1016/j.bbadis.2011.03.016
37. [37]
  Ł. Gutowski, S. Kanikowski, D. Formanowicz, Life 13 (2023) 1690. doi: 10.3390/life13081690
38. [38]
  V. Mariaule, A. Kriaa, S. Soussou, et al., Int. J. Mol. Sci. 22 (2021) 2817. doi: 10.3390/ijms22062817
39. [39]
  M. Prakash, M.N. Chandraprabha, R. Hari Krishna, et al., Appl. Surf. Sci. Adv. 19 (2024) 100540. doi: 10.1016/j.apsadv.2023.100540
40. [40]
  R. Niu, J. Lan, D. Liang, et al., Cell Commun. Signal. 22 (2024) 474. doi: 10.1186/s12964-024-01836-y
41. [41]
  Y. Portilla, V. Mulens-Arias, N. Daviu, et al., ACS Appl. Mater. Interfaces 15 (2023) 35906–35926. doi: 10.1021/acsami.3c05555
42. [42]
  J. Nowak-Jary, B. Machnicka, Int. J. Nanomedicine 18 (2023) 4067–4100. doi: 10.2147/ijn.s415063
43. [43]
  H.S. Ouandaogo, S. Diallo, E. Odari, J. Kinyu, PLoS One 19 (2024) e0295463. doi: 10.1371/journal.pone.0295463
44. [44]
  H. Pang, Y. Wu, Y. Chen, et al., Drug Deliv. Transl. Res. 14 (2024) 2345–2355. doi: 10.1007/s13346-023-01504-7
45. [45]
  Y. Wang, L. Chen, Y. Wang, et al., J. Nanobiotechnology 21 (2023) 408.
46. [46]
  M. Chehelgerdi, M. Chehelgerdi, O.Q.B. Allela, et al., Mol. Cancer 22 (2023) 169.
47. [47]
  R. Liam-Or, F.N. Faruqu, A. Walters, et al., Nat. Nanotechnol. 19 (2024) 846–855. doi: 10.1038/s41565-023-01585-y
48. [48]
  F. Veider, E. Sanchez Armengol, A. Bernkop-Schnürch, Small 20 (2024) e2304713. doi: 10.1002/smll.202304713
49. [49]
  Z. Li, Y. Zhu, J.B. Matson, ACS Appl. Bio Mater. 5 (2022) 4635–4651. doi: 10.1021/acsabm.2c00188
50. [50]
  H.L. Huang, C.H. Lai, W.H. Tsai, et al., Life Sci. 337 (2024) 122379. doi: 10.1016/j.lfs.2023.122379
51. [51]
  C. Hu, G. He, Y. Yang, et al., Adv. Sci. 11 (2024) e2306070.
52. [52]
  T. Stalder, T. Zaiter, W. El-Basset, et al., Toxicology 481 (2022) 153353.
53. [53]
  C. Gunawan, M. Lim, C.P. Marquis, R. Amal, J. Mater. Chem. B 2 (2014) 2060–2083. doi: 10.1039/c3tb21526a
54. [54]
  C. Marques, G. Borchard, O. Jordan, Int. J. Pharm. 654 (2024) 123987. doi: 10.1016/j.ijpharm.2024.123987
55. [55]
  C. Pavón, E.M. Benetti, F. Lorandi, Langmuir 40 (2024) 11843–11857. doi: 10.1021/acs.langmuir.4c00956
56. [56]
  M. Salehipour, S. Rezaei, J. Mosafer, et al., J. Nanopart. Res. 23 (2021) 48.
57. [57]
  G.M. Manoj, M. Shalini, K. Thenmozhi, et al., Appl. Surf. Sci. Adv. 21 (2024) 100608.
58. [58]
  A.X.X. Tan, B.Y.C. Ong, T. Dinesh, D.K. Srinivasan, Int. J. Mol. Sci. 26 (2025) 6465. doi: 10.3390/ijms26136465
59. [59]
  S. Kaitha, M. Bashir, T. Ali, World J. Gastrointest. Pathophysiol. 6 (2015) 62–72. doi: 10.4291/wjgp.v6.i3.62
1. [1]
  Yixin Zhang , Ting Wang , Jixiang Zhang , Pengyu Lu , Neng Shi , Liqiang Zhang , Weiran Zhu , Nongyue He . Formation mechanism for stable system of nanoparticle/protein corona and phospholipid membrane. Chinese Chemical Letters, 2024, 35(4): 108619-. doi: 10.1016/j.cclet.2023.108619
2. [2]
  Linzhou Yin , Xiaowen Jiang , Miao Wang , Yiren Yang , Zhonggui He , Jin Sun , Huiyuan Gao , Mengchi Sun . Phytoconstituent-derived nano-medicines/vesicles providing a promising dawn for inflammatory bowel disease. Chinese Chemical Letters, 2025, 36(6): 110224-. doi: 10.1016/j.cclet.2024.110224
3. [3]
  Zeyu Li , Huan Shen , Wenli Cai , Quangang Xu , Wei Xia , Keke Ning , Ergang Liu , Yongzhuo Huang . Colon-targeted pellets encapsulating patchouli oil cocrystal for inflammatory bowel disease treatment. Chinese Chemical Letters, 2026, 37(5): 111292-. doi: 10.1016/j.cclet.2025.111292
4. [4]
  Luqing Zhao , Dan Dou , Di Zhang , Shuqing Wang , Xihan Zhu , Ning Ding , Shengsheng Zhang , Chao Li . Nanotechnology-based natural remedies: Advancing inflammatory bowel disease treatment through targeted drug delivery. Chinese Chemical Letters, 2026, 37(5): 111262-. doi: 10.1016/j.cclet.2025.111262
5. [5]
  Yeqi Huang , Yue Gao , Yuxin Lin , Yihao Li , Si Xiong , Xia Guo , Chuanbin Wu , Xin Pan , Wenhao Wang , Ziyu Zhao , Zhengwei Huang . “Connect” or “drag”? The impact of physiologically relevant inorganic ion pairs on the protein corona adsorption onto liposomes. Chinese Chemical Letters, 2026, 37(2): 111014-. doi: 10.1016/j.cclet.2025.111014
6. [6]
  Yihao He , Ru Guo , Lu Yang , Ling Li , Tong Zhang , Bing Wang , Yongzhuo Huang . Phospholipid complex-based microemulsion for treating concurrence of primary sclerosing cholangitis and inflammatory bowel disease via gut-liver crosstalk. Chinese Chemical Letters, 2025, 36(10): 110778-. doi: 10.1016/j.cclet.2024.110778
7. [7]
  Jun-Yang Wang , Yu-Qing Wei , Qing-Ning Wang , Zhi-Guo Wang , Rui Hong , Lisha Yi , Ping Xu , Jia-Zhuang Xu , Zhong-Ming Li , Baisong Zhao . Mucus-inspired lubricative antibacterial coating to reduce airway complications in an intubation cynomolgus monkey model. Chinese Chemical Letters, 2025, 36(8): 110559-. doi: 10.1016/j.cclet.2024.110559
8. [8]
  Jiaqi Liu , Sishi Li , Yandong Xie , Ziqiang Fan , Zhenyuan Miao , Pengwei Jing , Yuecong Chen , Jian Zhu , Chao Yang , Xingbin Yan . Surface engineering driven performance optimization of hard carbon for sodium ion storage. Chinese Chemical Letters, 2026, 37(7): 111112-. doi: 10.1016/j.cclet.2025.111112
9. [9]
  Rui Li , Ruijie Lu , Libin Yang , Jianwen Li , Zige Guo , Qiquan Yan , Mengjun Li , Yazhuo Ni , Keying Chen , Yaoyang Li , Bo Xu , Mengzhen Cui , Zhan Li , Zhiying Zhao . Immobilization of chitosan nano-hydroxyapatite alendronate composite microspheres on polyetheretherketone surface to enhance osseointegration by inhibiting osteoclastogenesis and promoting osteogenesis. Chinese Chemical Letters, 2025, 36(4): 110242-. doi: 10.1016/j.cclet.2024.110242
10. [10]
  Kai Li , Hui Fang , Feixia Ruan , Xiaochun Xie , Huicong Zhou , Zhenjun Luo , Dan Shao , Mingqiang Li , Qing Yuan , Fangman Chen , Yu Tao . ROS-neutralizing surface engineering protects immunotoxicity of organic nanoscintillator-directed radiodynamic therapy. Chinese Chemical Letters, 2025, 36(12): 111261-. doi: 10.1016/j.cclet.2025.111261
11. [11]
  Caiwei Wang , Cheng Zeng , Changhong Wei , Guizhen Chen , Yueling Liang , Wenli Zhang . Lignin valorization towards porous carbon cathodes in zinc ion hybrid capacitors. Chinese Chemical Letters, 2026, 37(4): 111850-. doi: 10.1016/j.cclet.2025.111850
12. [12]
  Yu-Yang Bi , Ling-Feng Zhang , Qiu Chen , Ming-Yuan Yang , Lei Xing , Hu-Lin Jiang , Xian-Wu Cheng . A heterogeneity-modulated hydrogel for acute and chronic colitis therapy. Chinese Chemical Letters, 2026, 37(8): 111836-. doi: 10.1016/j.cclet.2025.111836
13. [13]
  Jianwen Zhao , Shuai Wang , Shanshan Zhao , Liwei Chen , Fangang Meng , Xuelin Tian . A non-fluorinated liquid-like membrane with excellent anti-scaling performance for membrane distillation. Chinese Chemical Letters, 2025, 36(1): 109883-. doi: 10.1016/j.cclet.2024.109883
14. [14]
  Haobo Wang , Fei Wang , Yong Liu , Zhongxiu Liu , Yingjie Miao , Wanhong Zhang , Guangxin Wang , Jiangtao Ji , Qiaobao Zhang . Emerging natural clay-based materials for stable and dendrite-free lithium metal anodes: A review. Chinese Chemical Letters, 2025, 36(2): 109589-. doi: 10.1016/j.cclet.2024.109589
15. [15]
  Zhenyang Yu , Yueyue Gu , Qi Sun , Yang Zheng , Yifang Zhang , Mengmeng Zhang , Delin Zhang , Zhijia Zhang , Yong Jiang . Research progress of modified metal current collectors in sodium metal anodes. Chinese Chemical Letters, 2025, 36(6): 109997-. doi: 10.1016/j.cclet.2024.109997
16. [16]
  Xinying Wang , Yuhang Fan , Xiyao Dong , Han Wu , Qingxiang Guan . Perspective and application advancements of chemically modified exosomes as novel tools for precise targeting in brain diseases: A strategic appraisal. Chinese Chemical Letters, 2026, 37(10): 112152-. doi: 10.1016/j.cclet.2025.112152
17. [17]
  Jingting Wang , Yuanyuan Chen , Linlin Han , Shasha Xia , Xingyao Zhang , Peng Xue , Yuejun Kang , Jian Ming , Zhigang Xu . Microenvironment responsive pod-structured astaxanthin nanocarrier for ameliorating inflammatory bowel disease. Chinese Chemical Letters, 2024, 35(7): 109029-. doi: 10.1016/j.cclet.2023.109029
18. [18]
  Junfei Yang , Ke Wang , Shuxin Sun , Tianqi Pei , Junxiu Li , Xunwei Gong , Cuixia Zheng , Yun Zhang , Qingling Song , Lei Wang . A "spore-like" oral nanodrug delivery platform for precision targeted therapy of inflammatory bowel disease. Chinese Chemical Letters, 2025, 36(3): 110180-. doi: 10.1016/j.cclet.2024.110180
19. [19]
  Wenbi Wu , Yinchu Dong , Haofan Liu , Xuebing Jiang , Li Li , Yi Zhang , Maling Gou . Modification of plasma protein for bioprinting via photopolymerization. Chinese Chemical Letters, 2024, 35(8): 109260-. doi: 10.1016/j.cclet.2023.109260
20. [20]
  Wenhao Wang , Siyuan Peng , Zhengwei Huang , Xin Pan . Tuning amino/hydroxyl ratios of nanovesicles to manipulate protein corona-mediated in vivo fate. Chinese Chemical Letters, 2024, 35(11): 110134-. doi: 10.1016/j.cclet.2024.110134

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(3)
HTML views(0)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142