Citation: Zhengzheng Lv, Xin Xia, Peisheng Cao, Qi Han, Hang Zhao, Ronghui Zhou, Peng Wu. Overcoming the drug retention barrier with photosensitive hydrogel for sustained photodynamic therapy of oral leukoplakia[J]. Chinese Chemical Letters, ;2026, 37(5): 111282. doi: 10.1016/j.cclet.2025.111282 shu

Overcoming the drug retention barrier with photosensitive hydrogel for sustained photodynamic therapy of oral leukoplakia

Zhengzheng Lv ^a ,
Xin Xia ^b ,
Peisheng Cao ^a ,
Qi Han ^c ,
Hang Zhao ^b ,
Ronghui Zhou ^{b, *,} ,
Peng Wu ^a

a.
Analytical & Testing Center, Sichuan University, Chengdu 610064, China
b.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
c.
West China Hospital of Stomatology, Oral Pathology, Sichuan University, Chengdu 610041, China

zhouronghui@scu.edu.cn

Received Date: 1 April 2025
Revised Date: 29 April 2025
Accepted Date: 30 April 2025
Available Online: 30 April 2025

Figures(5)

Oral leukoplakia (OLK) is a common and representative malignant disease of oral mucosa, and possess a higher risk of cancer. Compared with traditional surgical treatment, photodynamic therapy (PDT) has great potential in OLK treatment, due to its advantages of minimally invasiveness and low toxic side effects. However, traditional photosensitizer administration suffers from short retention time due to the fluid environment of saliva and extensive tongue movement, leading to poor drug (photosensitizer) utilization and limited therapeutic outcome. To address such issue, here a photosensitive guanosine (G)-based hydrogel system (G@GQD) was constructed, in which graphene quantum dots (GQDs) featuring high photosensitization activity was loaded through three dimensional (3D) fiber network physical encapsulation. The favorable adhesion of the G@GQD hydrogel on the tongue, together with sustained GQDs release, significantly enhanced the retention of GQDs within the oral cavity. As a result, G@GQD hydrogel could continuously generate high levels of reactive oxygen species (ROS) under irradiation, demonstrating a sustained therapeutic efficiency in vitro. Compared with free GQDs, G@GQD exhibited significantly improved PDT efficiency in treating 4-nitroquinoline 1-oxide (4-NQO)-induced OLK animals. This study presented a promising strategy in overcoming the drug retention barrier that caused by saliva and tongue movement, which has far-reaching significance for the future PDT therapies.
- Oral leukoplakia,
- Photosensitive hydrogel,
- Graphene quantum dots,
- Drug retention time,
- Sustained photodynamic therapy
1. [1]
  S. Petti, Oral Oncol. 39 (2003) 770–780. doi: 10.1016/S1368-8375(03)00102-7
2. [2]
  S. Warnakulasuriya, A. Ariyawardana, J. Oral Pathol. Med. 45 (2016) 155–166. doi: 10.1111/jop.12339
3. [3]
  M. Lyu, Y. Guo, S. Li, D. Yang, H. Hua, Int. Dent. J. 67 (2017) 252–259. doi: 10.1111/idj.12292
4. [4]
  P. Agostinis, K. Berg, K.A. Cengel, et al., CA Cancer J. Clin. 61 (2011) 250–281. doi: 10.3322/caac.20114
5. [5]
  M. Lan, S. Zhao, W. Liu, Adv. Healthc. Mater. 8 (2019) 1900132. doi: 10.1002/adhm.201900132
6. [6]
  R. Zhou, X. Zeng, H. Zhao, Q. Chen, P. Wu, Coord. Chem. Rev. 452 (2022) 214306. doi: 10.1016/j.ccr.2021.214306
7. [7]
  Z. Gao, X. Zheng, W. Liu, et al., Chin. Chem. Lett. 36 (2025) 109874. doi: 10.1016/j.cclet.2024.109874
8. [8]
  M. Pietruska, S. Sobaniec, P. Bernaczyk, Photodiagn. Photodyn. Ther. 11 (2014) 34–40. doi: 10.1016/j.pdpdt.2013.10.003
9. [9]
  Q. Chen, H. Dan, F. Tang, Int. J. Oral Sci. 11 (2019) 14. doi: 10.1557/mrc.2018.191
10. [10]
  X. Jin, H. Xu, J. Deng, Photodiagn. Photodyn. Ther. 28 (2019) 146–152. doi: 10.1016/j.pdpdt.2019.08.005
11. [11]
  D. Yang, Y. Song, J. Liu, et al., J. Dent. Res. 103 (2024) 1227–1237. doi: 10.1177/00220345241280257
12. [12]
  Y. Tao, C. Yan, Y. Wu, Adv. Funct. Mater. 33 (2023) 2303240. doi: 10.1002/adfm.202303240
13. [13]
  M. Avila, D.M. Ojcius, Ö. Yilmaz, DNA Cell Biol. 28 (2009) 405–411. doi: 10.1089/dna.2009.0874
14. [14]
  C. Cui, L. Mei, D. Wang, Nat. Commun. 14 (2023) 7707. doi: 10.1038/s41467-023-43571-x
15. [15]
  Y. Wu, Z. Wang, Y. Ge, J. Control. Release 370 (2024) 747–762. doi: 10.3390/cryst14080747
16. [16]
  L. Xie, X. Zhang, X. Wang, et al., Chin. Chem. Lett. 36 (2025) 110848. doi: 10.1016/j.cclet.2025.110848
17. [17]
  G. Fang, X. Yang, S. Chen, Coord. Chem. Rev. 454 (2022) 214352. doi: 10.1016/j.ccr.2021.214352
18. [18]
  A.N. Zelikin, C. Ehrhardt, A.M. Healy, Nat. Chem. 8 (2016) 997–1007. doi: 10.1038/nchem.2629
19. [19]
  S. Bernhard, M.W. Tibbitt, Adv. Drug Deliv. Rev. 171 (2021) 240–256. doi: 10.1016/j.addr.2021.02.002
20. [20]
  M.J. Webber, R. Langer, Chem. Soc. Rev. 46 (2017) 6600–6620. doi: 10.1039/C7CS00391A
21. [21]
  J.T. Davis, G.P. Spada, Chem. Soc. Rev. 36 (2007) 296–313. doi: 10.1039/B600282J
22. [22]
  G.M. Peters, L.P. Skala, T.N. Plank, J. Am. Chem. Soc. 137 (2015) 5819–5827. doi: 10.1021/jacs.5b02753
23. [23]
  R. Nishiyabu, Y. Kubo, T.D. James, J.S. Fossey, Chem. Commun. 47 (2011) 1124–1150. doi: 10.1039/C0CC02921A
24. [24]
  H. Zhao, H. Feng, J. Liu, Biomaterials 230 (2020) 119598. doi: 10.1016/j.biomaterials.2019.119598
25. [25]
  X. Xia, S. Song, Y. Wen, Biomater. Sci. 11 (2023) 3092–3103. doi: 10.1039/d3bm00057e
26. [26]
  J. Qi, T. Ding, T. Liu, Adv. Funct. Mater. 32 (2022) 2204273. doi: 10.1002/adfm.202204273
27. [27]
  L. Zhang, L. Lei, Z. Zhao, et al., Chin. Chem. Lett. 36 (2025) 110316. doi: 10.1016/j.cclet.2024.110316
28. [28]
  L. Hu, C. Song, H. Li, Macromol. Biosci. 24 (2024) 2200565. doi: 10.1002/mabi.202200565
29. [29]
  Y. Li, S. Wu, J. Zhang, R. Zhou, X. Cai, Cell Prolif. 53 (2020) e12821. doi: 10.1111/cpr.12821
30. [30]
  J. Ge, M. Lan, B. Zhou, Nat. Commun. 5 (2014) 4596. doi: 10.1038/ncomms5596
31. [31]
  R. Zhou, X. Lu, Q. Yang, P. Wu, Chin. Chem. Lett. 30 (2019) 1843–1848. doi: 10.1016/j.cclet.2019.07.062
32. [32]
  S. Wu, X. Xia, R. Zhou, H. Zhao, Macromolecules 56 (2023) 5813–5824. doi: 10.1021/acs.macromol.3c00505
33. [33]
  H.L.D. Hayes, R. Wei, M. Assante, J. Am. Chem. Soc. 143 (2021) 14814–14826. doi: 10.1021/jacs.1c06863
34. [34]
  G.M. Peters, L.P. Skala, T.N. Plank, J. Am. Chem. Soc. 136 (2014) 12596–12599. doi: 10.1021/ja507506c
35. [35]
  D.M. Gray, J.D. Wen, C.W. Gray, Chirality 20 (2008) 431–440. doi: 10.1002/chir.20455
36. [36]
  S. Masiero, R. Trotta, S. Pieraccini, Org. Biomol. Chem. 8 (2010) 2683–2692. doi: 10.1039/c003428b
37. [37]
  Y. Li, L. Su, Y. Zhang, Adv. Sci. 9 (2022) 2103485.
38. [38]
  K. Matsumura, K. Tateno, Y. Tsuchido, H. Kawai, ChemPlusChem 86 (2021) 1421–1425. doi: 10.1002/cplu.202100407
39. [39]
  G.D. Cha, W.H. Lee, S.H. Sunwoo, ACS Nano 16 (2022) 554–567. doi: 10.1021/acsnano.1c07649
40. [40]
  S. Ran, L. Xue, X. Wei, J. Mater. Chem. B 12 (2024) 6005–6032. doi: 10.1039/d3tb03070a
41. [41]
  Y. Guan, Y. Zhang, Chem. Soc. Rev. 42 (2013) 8106–8121. doi: 10.1039/c3cs60152h
42. [42]
  T. Liu, Y. Du, Y. Yan, Mater. Today 62 (2023) 71–97.
43. [43]
  X. Wang, O. Ronsin, B. Gravez, Adv. Sci. 8 (2021) 2004213. doi: 10.1002/advs.202004213
44. [44]
  M.P. Murphy, H. Bayir, V. Belousov, Nat. Metab. 4 (2022) 651–662. doi: 10.1038/s42255-022-00591-z
45. [45]
  Q. Ning, Y. Zhang, H. Sun, et al., Chin. Chem. Lett. 36 (2025) 111133. doi: 10.1016/j.cclet.2025.111133
46. [46]
  L. Zhao, J. Li, G. Chen, et al., Chin. Chem. Lett. 37 (2026) 110959. doi: 10.1016/j.cclet.2025.110959
47. [47]
  D. Kanojia, M.M. Vaidya, Oral Oncol. 42 (2006) 655–667.
1. [1]
  Tong Zhao , Ke Wang , Feiyu Liu , Shiyu Zhang , Shih-Hsin Ho . Recent progress of tailoring valuable graphene quantum dots from biomass. Chinese Chemical Letters, 2025, 36(6): 110321-. doi: 10.1016/j.cclet.2024.110321
2. [2]
  Manman Ou , Yunjian Zhu , Jiahao Liu , Zhaoxuan Liu , Jianjun Wang , Jun Sun , Chuanxiang Qin , Lixing Dai . Polyvinyl alcohol fiber with enhanced strength and modulus and intense cyan fluorescence based on covalently functionalized graphene quantum dots. Chinese Chemical Letters, 2025, 36(2): 110510-. doi: 10.1016/j.cclet.2024.110510
3. [3]
  Jiechen Liu , Xiaoguang Li , Ruiyang Xia , Yuqi Wang , Fenghe Zhang , Yongzhi Pang , Qing Li . Efficient suppression of oral squamous cell carcinoma through spatial dimension conversion drug delivery systems-enabled immunomodulatory-photodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109619-. doi: 10.1016/j.cclet.2024.109619
4. [4]
  Xi Chen , Xue Zhang , Shuai Yang , Jie Wang , Tian Tang , Maling Gou . An adhesive hydrogel for the treatment of oral ulcers. Chinese Chemical Letters, 2025, 36(3): 110021-. doi: 10.1016/j.cclet.2024.110021
5. [5]
  Mingrui Zhang , Lingyu Jin , Yuda Zhu , Junfeng Kou , Bo Liu , Jing Chen , Xiaolin Zhong , Xianghua Wu , Junfeng Zhang , Wenxiu Ren . A near-infrared Ⅱ fluorescent dye based on oxanthracene: Real-time imaging of drug-induced acute liver injury and photothermal therapy for tumor. Chinese Chemical Letters, 2025, 36(10): 110772-. doi: 10.1016/j.cclet.2024.110772
6. [6]
  Junqing Ye , Mengyuan Ren , Junfeng Qian , Xibao Li , Qun Chen . Advances in graphene quantum dots-based photocatalysts for enhanced charge transfer in photocatalytic reactions. Chinese Chemical Letters, 2025, 36(9): 110857-. doi: 10.1016/j.cclet.2025.110857
7. [7]
  Ningyue Xu , Jun Wang , Lei Liu , Changyang Gong . Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy: A review of recent advances. Chinese Chemical Letters, 2024, 35(8): 109225-. doi: 10.1016/j.cclet.2023.109225
8. [8]
  Jia-Qi Feng , Xiang Tian , Rui-Ge Cao , Yong-Xiu Li , Wen-Long Liu , Rong Huang , Si-Yong Qin , Ai-Qing Zhang , Yin-Jia Cheng . An AIE-based theranostic nanoplatform for enhanced colorectal cancer therapy: Real-time tumor-tracking and chemical-enhanced photodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109657-. doi: 10.1016/j.cclet.2024.109657
9. [9]
  Linghui Zou , Meng Cheng , Kaili Hu , Jianfang Feng , Liangxing Tu . Vesicular drug delivery systems for oral absorption enhancement. Chinese Chemical Letters, 2024, 35(7): 109129-. doi: 10.1016/j.cclet.2023.109129
10. [10]
  Fengjie Liu , Fansu Meng , Zhenjiang Yang , Huan Wang , Yuehong Ren , Yu Cai , Xingwang Zhang . Exosome-biomimetic nanocarriers for oral drug delivery. Chinese Chemical Letters, 2024, 35(9): 109335-. doi: 10.1016/j.cclet.2023.109335
11. [11]
  Yu Si , Xueying Jiang , Zhigang Gao , Yuan Liang , Wen Sun , Engin U. Akkaya , Lei Wang . NIR light-activated programmable drug immobilization and oxygen modulation for enhanced photodynamic and chemo-therapy. Chinese Chemical Letters, 2026, 37(3): 111195-. doi: 10.1016/j.cclet.2025.111195
12. [12]
  Hao Cai , Xiaoyan Wu , Lei Jiang , Feng Yu , Yuxiang Yang , Yan Li , Xian Zhang , Jian Liu , Zijian Li , Hong Bi . Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy. Chinese Chemical Letters, 2024, 35(4): 108946-. doi: 10.1016/j.cclet.2023.108946
13. [13]
  Quanxin Ning , Yidan Zhang , Huayi Sun , Xin Zhao , Haodong Zhang , Feng Cui , Xiaochun Xie , Fangman Chen , Wen Sun , Hong Zhang . Light-harvesting pigment-binding protein-mimicking carbon dots for photodynamic therapy. Chinese Chemical Letters, 2025, 36(11): 111133-. doi: 10.1016/j.cclet.2025.111133
14. [14]
  Leichen Wang , Anqing Mei , Na Li , Xiaohong Ruan , Xu Sun , Yu Cai , Jinjun Shao , Xiaochen Dong . Aza-BODIPY dye with unexpected bromination and high singlet oxygen quantum yield for photoacoustic imaging-guided synergetic photodynamic/photothermal therapy. Chinese Chemical Letters, 2024, 35(6): 108974-. doi: 10.1016/j.cclet.2023.108974
15. [15]
  Zhuan Chen , Bo Yang , Jun Li , Kun Du , Jiangchen Fu , Xiao Wu , Jiazhen Cao , Mingyang Xing . Environmentally safe storage and sustained release of hydrogen peroxide utilizing commercial hydrogel. Chinese Chemical Letters, 2025, 36(6): 110320-. doi: 10.1016/j.cclet.2024.110320
16. [16]
  Mengyu Chen , Qinglin Zhou , Tianyun Qin , Ningyao Sun , Yuxi Chen , Yuwei Gong , Xingyi Li , Jinsong Liu . An ionic liquid-reinforced gelatin hydrogel with strong adhesion, antibacterial and anti-inflammatory properties for treating oral ulcers. Chinese Chemical Letters, 2025, 36(7): 110441-. doi: 10.1016/j.cclet.2024.110441
17. [17]
  Zheyi Li , Xiaoyang Liang , Zitong Qiu , Zimeng Liu , Siyu Wang , Yue Zhou , Nan Li . Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel. Chinese Chemical Letters, 2024, 35(11): 109592-. doi: 10.1016/j.cclet.2024.109592
18. [18]
  Siting Cai , Xiang Chen , Shuli Wang , Xinqin Liao , Zhong Chen , Yue Lin . Silica coating of quantum dots and their applications in optoelectronic fields. Chinese Chemical Letters, 2025, 36(6): 110798-. doi: 10.1016/j.cclet.2024.110798
19. [19]
  Yuyao Guan , Baoting Yu , Jun Ding , Tingting Sun , Zhigang Xie . BODIPY photosensitizers for antibacterial photodynamic therapy. Chinese Chemical Letters, 2025, 36(8): 110645-. doi: 10.1016/j.cclet.2024.110645
20. [20]
  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

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(7)
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