Citation: Xiangjun Zhang, Xiaodi Yang, Yan Wang, Zhongping Xu, Sisi Yi, Tao Guo, Yue Liao, Xiyu Tang, Jianxiang Zhang, Ruibing Wang. A supramolecular nanoprodrug for prevention of gallstone formation[J]. Chinese Chemical Letters, ;2025, 36(2): 109854. doi: 10.1016/j.cclet.2024.109854 shu

A supramolecular nanoprodrug for prevention of gallstone formation

Xiangjun Zhang ^{a, *,} ,
Xiaodi Yang ^a ,
Yan Wang ^a ,
Zhongping Xu ^b ,
Sisi Yi ^a ,
Tao Guo ^a ,
Yue Liao ^a ,
Xiyu Tang ^a ,
Jianxiang Zhang ^{c, d, e, *,} ,
Ruibing Wang ^{f, *,}

a.
College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
b.
Chongqing University Fuling Hospital, Chongqing 408000, China
c.
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China
d.
Yu-Yue Pathology Scientific Research Center, Chongqing 400039, China
e.
State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing 400038, China
f.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China

xiangjunzhang@cqmu.edu.cn

jxzhang@tmmu.edu.cn

rwang@um.edu.mo

Received Date: 9 January 2024
Revised Date: 24 March 2024
Accepted Date: 2 April 2024
Available Online: 2 April 2024

Figures(4)

Cholelithiasis affects approximately 10%-20% of the adult population globally. And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones. Hydroxypropyl-β-cyclodextrin (HPCD) is a supramolecular host compound that can solubilize cholesterol, potentially serving as a preventative or therapeutic agent for cholelithiasis. However, we found that the administration of HPCD treatment did not impede the formation of gallstones in mice, mainly attributed to the pre-complexation of its cavity during the transition process. Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle (HPCD-NP), which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection. In the bile, the HPCD-NP degraded into free HPCD, bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization, leading to gallstones regression. Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies, HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.
- Gallstone,
- Hydroxypropyl-β-cyclodextrin,
- Hepatobiliary transport,
- Host-guest interaction,
- Solubilization
1. [1]
  P. Portincasa, A. Moschetta, G. Palasciano, Lancet 368 (2006) 230–239. doi: 10.1016/S0140-6736(06)69044-2
2. [2]
  K.S. Gurusamy, B.R. Davidson, Br. Med. J. 348 (2014) g2669. doi: 10.1136/bmj.g2669
3. [3]
  F. Lammert, K. Gurusamy, C.W. Ko, et al., Nat. Rev. Dis. Primers 2 (2016) 16024. doi: 10.1038/nrdp.2016.24
4. [4]
  P. Portincasa, A. Di Ciaula, O. de Bari, et al., Expert Rev. Gastroenterol. Hepatol. 10 (2016) 93–112. doi: 10.1586/17474124.2016.1109445
5. [5]
  X. Zhao, N. Wang, Y. Sun, et al., Liver Int. 40 (2020) 1744–1755. doi: 10.1111/liv.14456
6. [6]
  E.S. Schernhammer, M.F. Leitzmann, D.S. Michaud, et al., Br. J. Cancer 88 (2003) 79–83. doi: 10.1038/sj.bjc.6600661
7. [7]
  A. Di Ciaula, G. Garruti, D.Q.H. Wang, P. Portincasa, Eur. J. Int. Med. 53 (2018) 3–11. doi: 10.1016/j.ejim.2018.04.019
8. [8]
  J.H. Oak, C.N. Paik, W.C. Chung, K.M. Lee, J.M. Yang, Gastroenterol. Res. Pract. 2012 (2012) 417821. doi: 10.1155/2012/417821
9. [9]
  P. Chowbey, A. Sharma, A. Goswami, et al., J. Minim. Access Surg. 11 (2015) 223–230. doi: 10.4103/0972-9941.158156
10. [10]
  S. Nakagawa, I. Makino, T. Ishizaki, I. Dohi, Lancet 310 (1977) 367–369. doi: 10.1016/S0140-6736(77)90301-4
11. [11]
  N. Villanova, F. Bazzoli, F. Taroni, et al., Gastroenterology 97 (1989) 726–731. doi: 10.1016/0016-5085(89)90644-6
12. [12]
  V.I. Reshetnyak, World J. Hepatol. 4 (2012) 18–34.
13. [13]
  N.G. Venneman, M.G. Besselink, Y.C. Keulemans, et al., Hepatology 43 (2006) 1276–1283. doi: 10.1002/hep.21182
14. [14]
  S. Haal, M.S.S. Guman, T.C.C. Boerlage, et al., Lancet Gastroenterol. Hepatol. 6 (2021) 993–1001. doi: 10.1016/S2468-1253(21)00301-0
15. [15]
  L. Hall, J. Halle-Smith, R. Evans, et al., BJS Open 7 (2023) zrac152. doi: 10.1093/bjsopen/zrac152
16. [16]
  N.G. Venneman, K.J. van Erpecum, Gastroenterol. Clin. 39 (2010) 171–183. doi: 10.1016/j.gtc.2010.02.010
17. [17]
  P. Jansook, N. Ogawa, T. Loftsson, Int. J. Pharm. 535 (2018) 272–284. doi: 10.1016/j.ijpharm.2017.11.018
18. [18]
  F. Zakany, T. Kovacs, L. Szente, Z. Varga, Cyclodextrins as promising therapeutics against cholesterol overload, in: A.N. Bukiya, A.M. Dopico (Eds.) Cholesterol, Academic Press, Elsevier Inc., 2022, pp. 927–967.
19. [19]
  R.O. Williams, V. Mahaguna, M. Sriwongjanya, Eur. J. Pharm. Biopharm. 46 (1998) 355–360. doi: 10.1016/S0939-6411(98)00033-2
20. [20]
  S. Zimmer, A. Grebe, S.S. Bakke, et al., Sci. Transl. Med. 8 (2016) 333–350. doi: 10.15375/9783814557748-012
21. [21]
  C.H. Vite, J.H. Bagel, G.P. Swain, et al., Sci. Transl. Med. 7 (2015) 276ra26-276ra26. doi: 10.1126/scitranslmed.3010101
22. [22]
  S.V. Kurkov, T. Loftsson, Int. J. Pharm. 453 (2013) 167–180. doi: 10.1016/j.ijpharm.2012.06.055
23. [23]
  F.L. Aachmann, K.L. Larsen, R. Wimmer, J. Inclusion Phenom. Macrocyclic Chem. 73 (2012) 349–357. doi: 10.1007/s10847-011-0071-y
24. [24]
  M. Mahjoubin-Tehran, P.T. Kovanen, S. Xu, T. Jamialahmadi, A. Sahebkar, Pharmacol. Ther. 214 (2020) 107620. doi: 10.1016/j.pharmthera.2020.107620
25. [25]
  W.C. Geng, J.L. Sessler, D.S. Guo, Chem. Soc. Rev. 49 (2020) 2303–2315. doi: 10.1039/c9cs00622b
26. [26]
  S.Y. Yao, Y.X. Yue, A.K. Ying, et al., Angew. Chem. Int. Ed. 62 (2023) e202213578. doi: 10.1002/anie.202213578
27. [27]
  Y.N. Zhang, W. Poon, A.J. Tavares, I.D. McGilvray, W.C.W. Chan, J. Control. Release 240 (2016) 332–348. doi: 10.1016/j.jconrel.2016.01.020
28. [28]
  W. Poon, Y.N. Zhang, B. Ouyang, et al., ACS Nano 13 (2019) 5785–5798. doi: 10.1021/acsnano.9b01383
29. [29]
  M.I. Eder, J.F. Miquel, D. Jüngst, G. Paumgartner, C. Von Ritter, Free Radic. Biol. Med. 20 (1996) 743–749. doi: 10.1016/0891-5849(95)02154-X
30. [30]
  L. Li, J. Guo, Y. Wang, et al., Adv. Sci. 5 (2018) 1800781. doi: 10.1002/advs.201800781
31. [31]
  Y. Wang, L. Li, W. Zhao, et al., ACS Nano 12 (2018) 8943–8960. doi: 10.1021/acsnano.8b02037
32. [32]
  D. Zhang, Y. Wei, K. Chen, et al., Adv. Healthc. Mater. 4 (2015) 69–76. doi: 10.1002/adhm.201400299
33. [33]
  K.E. Broaders, S. Grandhe, J.M. Frechet, J. Am. Chem. Soc. 133 (2011) 756–758. doi: 10.1021/ja110468v
34. [34]
  I. Ui, A. Okajo, K. Endo, H. Utsumi, K.I. Matsumoto, Free Radic. Biol. Med. 37 (2004) 2012–2017. doi: 10.1016/j.freeradbiomed.2004.09.012
35. [35]
  S. Koppisetti, B. Jenigiri, M.P. Terron, et al., Dig. Dis. Sci. 53 (2008) 2592–2603. doi: 10.1007/s10620-007-0195-5
36. [36]
  N. Kaeokhamloed, S. Legeay, E. Roger, J. Control. Release 349 (2022) 156–173. doi: 10.1016/j.jconrel.2022.06.048
1. [1]
  Jie Yang , Xin-Yue Lou , Dihua Dai , Jingwei Shi , Ying-Wei Yang . Desymmetrized pillar[8]arenes: High-yield synthesis, functionalization, and host-guest chemistry. Chinese Chemical Letters, 2025, 36(1): 109818-. doi: 10.1016/j.cclet.2024.109818
2. [2]
  Lijun Mao , Shuo Li , Xin Zhang , Zhan-Ting Li , Da Ma . Cucurbit[n]uril-based nanostructure construction and modification. Chinese Chemical Letters, 2024, 35(8): 109363-. doi: 10.1016/j.cclet.2023.109363
3. [3]
  Shuo Li , Qianfa Liu , Lijun Mao , Xin Zhang , Chunju Li , Da Ma . Benzothiadiazole-based water-soluble macrocycle: Synthesis, aggregation-induced emission and selective detection of spermine. Chinese Chemical Letters, 2024, 35(11): 109791-. doi: 10.1016/j.cclet.2024.109791
4. [4]
  Jianmei Guo , Yupeng Zhao , Lei Ma , Yongtao Wang . Ultra-long room temperature phosphorescence, intrinsic mechanisms and application based on host-guest doping systems. Chinese Journal of Structural Chemistry, 2024, 43(9): 100335-100335. doi: 10.1016/j.cjsc.2024.100335
5. [5]
  Cheng Wang , Ji Wang , Dong Liu , Zhi-Ling Zhang . Advances in virus-host interaction research based on microfluidic platforms. Chinese Chemical Letters, 2024, 35(12): 110302-. doi: 10.1016/j.cclet.2024.110302
6. [6]
  Bingbing Shi , Yuchun Wang , Yi Zhou , Xing-Xing Zhao , Yizhou Li , Nuoqian Yan , Wen-Juan Qu , Qi Lin , Tai-Bao Wei . A supramolecular oligo[2]rotaxane constructed by orthogonal platinum(Ⅱ) metallacycle and pillar[5]arene-based host–guest interactions. Chinese Chemical Letters, 2024, 35(10): 109540-. doi: 10.1016/j.cclet.2024.109540
7. [7]
  Xianchen Hu , Junli Yang , Fang Gao , Zhiyong Zhao , Simin Liu . Highly selective [4+4] cross-photodimerization of (4a-azonia)anthracenes driven by confinement of D-A hetero-guest pair in cucurbit[10]uril host. Chinese Chemical Letters, 2025, 36(3): 109967-. doi: 10.1016/j.cclet.2024.109967
8. [8]
  Yinglan Yu , Sajid Hussain , Jianping Qi , Lei Luo , Xuemei Zhang . Mechanisms and applications: Cargos transport to basolateral membranes in polarized epithelial cells. Chinese Chemical Letters, 2024, 35(12): 109673-. doi: 10.1016/j.cclet.2024.109673
9. [9]
  Jia-hui Li , Jinkai Qiu , Cheng Lian . Lithium-ion rapid transport mechanism and channel design in solid electrolytes. Chinese Journal of Structural Chemistry, 2025, 44(1): 100381-100381. doi: 10.1016/j.cjsc.2024.100381
10. [10]
  Qinwei Lu , Jinjie Lu , Juying Lei , Xubiao Luo , Yanbo Zhou . Cyclodextrin-boosted photocatalytic oxidation for efficient bisphenol A removal. Chinese Chemical Letters, 2025, 36(3): 110017-. doi: 10.1016/j.cclet.2024.110017
11. [11]
  Kai Han , Guohui Dong , Ishaaq Saeed , Tingting Dong , Chenyang Xiao . Boosting bulk charge transport of CuWO4 photoanodes via Cs doping for solar water oxidation. Chinese Journal of Structural Chemistry, 2024, 43(2): 100207-100207. doi: 10.1016/j.cjsc.2023.100207
12. [12]
  Rongjun Zhao , Tai Wu , Yong Hua , Yude Wang . Improving performance of perovskite solar cells enabled by defects passivation and carrier transport dynamics regulation via organic additive. Chinese Chemical Letters, 2025, 36(2): 109587-. doi: 10.1016/j.cclet.2024.109587
13. [13]
  Shaonan Liu , Shuixing Dai , Minghua Huang . The impact of ester groups on 1,8-naphthalimide electron transport material in organic solar cells. Chinese Journal of Structural Chemistry, 2024, 43(6): 100277-100277. doi: 10.1016/j.cjsc.2024.100277
14. [14]
  Siwei Wang , Wei-Lei Zhou , Yong Chen . Cucurbituril and cyclodextrin co-confinement-based multilevel assembly for single-molecule phosphorescence resonance energy transfer behavior. Chinese Chemical Letters, 2024, 35(12): 110261-. doi: 10.1016/j.cclet.2024.110261
15. [15]
  Zhibin Ren , Shan Li , Xiaoying Liu , Guanghao Lv , Lei Chen , Jingli Wang , Xingyi Li , Jiaqing Wang . Penetrating efficiency of supramolecular hydrogel eye drops: Electrostatic interaction surpasses ligand-receptor interaction. Chinese Chemical Letters, 2024, 35(11): 109629-. doi: 10.1016/j.cclet.2024.109629
16. [16]
  Yue Zheng , Tianpeng Huang , Pengxian Han , Jun Ma , Guanglei Cui . Cathodal Li-ion interfacial transport in sulfide-based all-solid-state batteries: Challenges and improvement strategies. Chinese Journal of Structural Chemistry, 2024, 43(10): 100390-100390. doi: 10.1016/j.cjsc.2024.100390
17. [17]
  Brandon Bishop , Shaofeng Huang , Hongxuan Chen , Haijia Yu , Hai Long , Jingshi Shen , Wei Zhang . Artificial transmembrane channel constructed from shape-persistent covalent organic molecular cages capable of ion and small molecule transport. Chinese Chemical Letters, 2024, 35(11): 109966-. doi: 10.1016/j.cclet.2024.109966
18. [18]
  Hao Zhang , Haonan Qu , Ehsan Bahojb Noruzi , Haibing Li , Feng Liang . A nanocomposite film with layer-by-layer self-assembled gold nanospheres driven by cucurbit[7]uril for the selective transport of L-tryptophan and lysozyme. Chinese Chemical Letters, 2025, 36(1): 109731-. doi: 10.1016/j.cclet.2024.109731
19. [19]
  Jiangqi Ning , Junhan Huang , Yuhang Liu , Yanlei Chen , Qing Niu , Qingqing Lin , Yajun He , Zheyuan Liu , Yan Yu , Liuyi Li . Alkyl-linked TiO2@COF heterostructure facilitating photocatalytic CO2 reduction by targeted electron transport. Chinese Journal of Structural Chemistry, 2024, 43(12): 100453-100453. doi: 10.1016/j.cjsc.2024.100453
20. [20]
  Wenjia Wang , Xingyue He , Xiaojie Wang , Tiantian Zhao , Osamu Muraoka , Genzoh Tanabe , Weijia Xie , Tianjiao Zhou , Lei Xing , Qingri Jin , Hulin Jiang . Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin (Ⅳ) prodrug delivery and enhanced colorectal cancer therapy. Chinese Chemical Letters, 2024, 35(4): 108656-. doi: 10.1016/j.cclet.2023.108656

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(194)
HTML views(14)

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