Antioxidant Glycopolypeptide Micelles for Targeted Delivery of Silibinin to Hepatocellular Carcinoma Cells

Kai Chen; Ping Wei; Jing-Hua Chen

doi:10.1007/s10118-025-3429-0

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Antioxidant Glycopolypeptide Micelles for Targeted Delivery of Silibinin to Hepatocellular Carcinoma Cells

RESEARCH ARTICLE | Updated：2025-10-30

- Antioxidant Glycopolypeptide Micelles for Targeted Delivery of Silibinin to Hepatocellular Carcinoma Cells
- Antioxidant Glycopolypeptide Micelles for Targeted Delivery of Silibinin to Hepatocellular Carcinoma Cells
- 高分子科学（英文） 2025年43卷第11期页码：2051-2060
- Affiliations：
  
  Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
- Author bio：
  
  weiping@jiangnan.edu.cn (P.W.)
  chenjinghua@jiangnan.edu.cn (J.H.C.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (No. 22305102), Basic Research Program of Jiangsu (No. BK20221097), and the Open Project of Key Laboratory of Carbohydrate Chemistry and Biotechnology (Jiangnan University), Ministry of Education (No. KLCCB-KF202405).;Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-025-3429-0.
- DOI：10.1007/s10118-025-3429-0
  中图分类号：
- 收稿：2025-06-24，
  
  录用：2025-08-08，
  
  网络出版：2025-10-11，
  
  纸质出版：2025-11-05
- Accepted：
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Chen, K.; Wei, P.; Chen, J. H. Antioxidant glycopolypeptide micelles for targeted delivery of silibinin to hepatocellular carcinoma cells. Chinese J. Polym. Sci. 2025, 43, 2051–2060

Kai Chen, Ping Wei, Jing-Hua Chen. Antioxidant Glycopolypeptide Micelles for Targeted Delivery of Silibinin to Hepatocellular Carcinoma Cells[J]. Chinese journal of polymer science, 2025, 43(11): 2051-2060.
Chen, K.; Wei, P.; Chen, J. H. Antioxidant glycopolypeptide micelles for targeted delivery of silibinin to hepatocellular carcinoma cells. Chinese J. Polym. Sci. 2025, 43, 2051–2060 DOI： 10.1007/s10118-025-3429-0.

Kai Chen, Ping Wei, Jing-Hua Chen. Antioxidant Glycopolypeptide Micelles for Targeted Delivery of Silibinin to Hepatocellular Carcinoma Cells[J]. Chinese journal of polymer science, 2025, 43(11): 2051-2060. DOI： 10.1007/s10118-025-3429-0.

摘要

A versatile glycopolypeptide micelle system

featuring intrinsic antioxidant activity and specific targeting capability toward hepatocellular carcinoma cells

was rationally designed. This system demonstrates synergistic antioxidant effects through the combined action of encapsulated silibinin and the antioxidant glycopolypeptide scaffold

indicating promising bioapplications in the treatment of oxidative stress-related liver diseases.

Abstract

Silibinin

a natural flavanone extracted from the milk thistle plant (

Silybum marianum

)

has been shown to have various therapeutic applications

including liver protection

antioxidant

anticancer

anti-inflammatory

and many other effects. However

silibinin exhibits poor oral absorbance and low bioavailability owing to its limited water solubility

which limits its therapeutic efficiency and further clinical translation. To address these issues

we propose an antioxidant glycopolypeptide micelle strategy to target the delivery of silibinin to enhance its solubility

bioavailability

and antioxidant activity. This versatile micelle self-assembled from a glycopolypeptide

-acetylgalactosamine-grafted poly(glutamic acid)-

block

-poly(tyrosine).

-acetylgalactosamine (GalNAc) is incorporated to enable liver targeting by selectively binding to the asialoglycoprotein receptor

which is overexpressed on hepatocellular carcinoma cells. The antioxidant polypeptide polytyrosine

as well as encapsulated silibinin

exhibits a synergistic reactive oxygen species (ROS) scavenging effect. The obtained results confirmed that silibinin can be effectively encapsulated into the glycopolypeptide micelles through self-assembly

achieving a loading efficiency and loading content of 96.6% and 42.9%

spectively. The silibinin-loaded glycopolypeptide micelles exhibited enhanced cellular uptake and a synergistic ROS scavenging effect in hepatocellular carcinoma cells. Overall

these antioxidant glycopolypeptide micelles hold promise as safe and efficient drug delivery systems for targeting hepatocellular carcinoma cells

potentially providing an effective strategy to enhance the bioavailability and antioxidant activity of silibinin.

关键词

Keywords

references

Huo, M.; Wang, H.; Zhang, Y.; Cai, H.; Zhang, P.; Li, L.; Zhou, J.; Yin, T. Co-delivery of silybin and paclitaxel by dextran-based nanoparticles for effective anti-tumor treatment through chemotherapy sensitization and microenvironment modulation. J. Control. Release 2020 , 321 , 198−210..

Selc, M.; Macova, R.; Babelova, A. Novel strategies enhancing bioavailability and therapeutical potential of silibinin for treatment of liver disorders. Drug Des., Dev. Ther. 2024 , 18 , 4629−4659..

Abenavoli, L.; Izzo, A. A.; Milic, N.; Cicala, C.; Santini, A.; Capasso, R. Milk thistle (silybum marianum): a concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother. Res. 2018 , 32 , 2202−2213..

Federico, A.; Dallio, M.; Loguercio, C. Silymarin/silybin and chronic liver disease: a marriage of many years. Molecules 2017 , 22 , 191..

Hecht, F.; Zocchi, M.; Alimohammadi, F.; Harris, I. S. Regulation of antioxidants in cancer. Mol. Cell 2024 , 84 , 23−33..

Stravitz, R. T.; Lee, W. M. Acute liver failure. Lancet 2019 , 394 , 869−881..

Zhang, H.; Ding, F.; Zhu, Z.; Sun, Q.; Yang, C. Engineered ionizable lipid nanoparticles mediated efficient siRNA delivery to macrophages for anti-inflammatory treatment of acute liver injury. Int. J. Pharm. 2023 , 631 , 122489..

Wang, Y. A.; Wei, H. C.; Li, K. Y.; Liu, L. R.; Zhu, Y. F.; Wang, X. Y.; Yan, J. H.; Yu, L. M.; Yan, X. F.; He, Z. Y. Ros-responsive dextran-phenylboronic acid-silibinin nanoparticles for targeting delivery of BAPTA-AM to effectively eliminate calcium overload-mediated inflammatory cascades and mitochondrial apoptosis: alleviating acute liver injury. Chem. Eng. J. 2024 , 480 , 148283..

Ghalehkhondabi, V.; Soleymani, M.; Fazlali, A. Folate-targeted nanomicelles containing silibinin as an active drug delivery system for liver cancer therapy. J. Drug Deliv. Sci. Technol. 2021 , 61 , 102157..

Zhao, J.; Qi, Y. F.; Yu, Y. R. STAT3: a key regulator in liver fibrosis. Ann. Hepatol. 2021 , 21 , 100224..

Ray, P. P.; Islam, M. A.; Islam, M. S.; Han, A.; Geng, P.; Aziz, M. A.; Al Mamun, A. A comprehensive evaluation of the therapeutic potential of silibinin: A ray of hope in cancer treatment. Front. Pharmacol. 2024 , 15 , 1349745..

Christodoulou, E.; Kechagia, I. A.; Tzimas, S.; Balafas, E.; Kostomitsopoulos, N.; Archontaki, H.; Dokoumetzidis, A.; Valsami, G. Serum and tissue pharmacokinetics of silibinin after per os and i.V. Administration to mice as a hp- β -cd lyophilized product. Int. J. Pharm. 2015 , 493 , 366−373..

Kuen, C. Y.; Fakurazi, S.; Othman, S. S.; Masarudin, M. J. Increased loading, efficacy and sustained release of silibinin, a poorly soluble drug using hydrophobically-modified chitosan nanoparticles for enhanced delivery of anticancer drug delivery systems. Nanomaterials 2017 , 7 , 379..

Zhao, T.; Maniglio, D.; Chen, J.; Chen, B.; Migliaresi, C. Development of pH-sensitive self-nanoemulsifying drug delivery systems for acid-labile lipophilic drugs. Chem. Phys. Lipids 2016 , 196 , 81−88..

Fischer, N.; Seo, E. J.; Efferth, T. Prevention from radiation damage by natural products. Phytomedicine 2018 , 47 , 192−200..

Surai, P. F. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants (Basel, Switzerland) 2015 , 4 , 204−247..

Cheng, J.; Teply, B. A.; Sherifi, I.; Sung, J.; Luther, G.; Gu, F. X.; Levy-Nissenbaum, E.; Radovic-Moreno, A. F.; Langer, R.; Farokhzad, O. C. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 2007 , 28 , 869−876..

Di Costanzo, A.; Angelico, R. Formulation strategies for enhancing the bioavailability of silymarin: the state of the art. Molecules 2019 , 24 , 2155..

Wei, P.; Chen, K.; Chen, J. H. Engineering an ultrasound-responsive glycopolymersome for hepatocyte-specific gene delivery. Biomacromolecules 2024 , 25 , 7838−7849..

Kumar, V.; Turnbull, W. B. Targeted delivery of oligonucleotides using multivalent protein–carbohydrate interactions. Chem. Soc. Rev. 2023 , 52 , 1273−1287..

Zhang, W.; Ge, Z.; Xiao, Y.; Liu, D.; Du, J. Antioxidant and immunomodulatory polymer vesicles for effective diabetic wound treatment through ROS scavenging and immune modulating. Nano Lett. 2024 , 24 , 9494−9504..

Yang, K.; Liu, D.; Teng, R.; Li, C.; Fan, Z.; Du, J. An antibacterial polypeptide coating prepared by in situ enzymatic polymerization for preventing delayed infection of implants. ACS Biomater. Sci. Eng. 2023 , 9 , 1900−1908..

[Hougland, J. L.; Darling, J.; Flynn, S., Protein posttranslational modification. In Molecular basis of oxidative stress , John Wiley & Sons, Ltd., Hoboken, 2013 ; p. 71..

Liu, D. Q.; Zhang, W. Q.; Fan, Z.; He, S. S.; Du, J. Z. A ferroptosis-inhibitive polypeptosome for synergistic management of acute kidney injury through antioxidation and iron binding. Adv. Funct. Mater. 2024 , 34 , 2409892..

Wei, P.; Chen, S.; Shi, J. Q.; Du, J. Z. Oxygen-generating polymer vesicles for enhanced sonodynamic tumor therapy. J. Control. Release 2023 , 353 , 975−987..

Wang, T.; Teng, R.; Wu, M.; Ge, Z.; Liu, Y.; Yang, B.; Li, C.; Fan, Z.; Du, J. A polypeptosome spray to heal antibiotic-resistant bacteria-infected wound by photocatalysis-induced metabolism-interference. ACS Nano 2024 , 18 , 35620−35631..

Cai, Z.; Yan, Y. S.; Zhou, J.; Yang, Y.; Zhang, Y.; Chen, J. H. Multifunctionalized brush-like glycopolymers with high affinity to p-selectin and antitumor metastasis activity. Biomacromolecules 2021 , 22 , 1177−1185..

Chen, S.; Cornel, E. J.; Du, J.-Z. Controlling membrane phase separation of polymersomes for programmed drug release. Chin. J. Polym. Sci. 2022 , 40 , 1006−1015..

Yang, Y. Y.; Chen, L. S.; Sun, M.; Wang, C. Y.; Fan, Z.; Du, J.-Z. Biodegradable polypeptide-based vesicles with intrinsic blue fluorescence for antibacterial visualization. Chinese J. Polym. Sci. 2021 , 39 , 1412−1420..

Xuan, J.; Pelletier, M.; Xia, H.; Zhao, Y. Ultrasound-induced disruption of amphiphilic block copolymer micelles. Macromol. Chem. Phys. 2011 , 212 , 498−506..

Wei, P.; Sun, M.; Yang, B.; Xiao, J.; Du, J. Ultrasound -responsive polymersomes capable of endosomal escape for efficient cancer therapy. J. Controlled Release 2020 , 322 , 81−94..

Xue, S.; Gu, X. L.; Zhang, J.; Sun, H. L.; Deng, C.; Zhong, Z. Y. Construction of small-sized, robust, and reduction-responsive polypeptide micelles for high loading and targeted delivery of chemotherapeutics. Biomacromolecules 2018 , 19 , 3586−3593..

Abdolamir, A.; Reyhaneh, N. M.; Azadeh, A.; Giada, S.; Kostas, P. Oxidative stress in liver pathophysiology and disease. Antioxidants 2023 , 12 , 1653..

Lai, W.; Zhang, J.; Sun, J.; Min, T.; Bai, Y.; He, J.; Cao, H.; Che, Q.; Guo, J.; Su, Z. Oxidative stress in alcoholic liver disease, focusing on proteins, nucleic acids, and lipids: a review. Int. J. Biol. Macromol. 2024 , 278 , 134809..

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