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使用硫醇-烯水凝胶进行双药递送的局部癌症治疗

Localized Cancer Treatment Using Thiol-Ene Hydrogels for Dual Drug Delivery.

作者信息

Sathi Devi Lakshmi, Gigliobianco Maria Rosa, Gabrielli Serena, Agas Dimitrios, Sabbieti Maria Giovanna, Morelli Maria Beatrice, Amantini Consuelo, Casadidio Cristina, Di Martino Piera, Censi Roberta

机构信息

School of Pharmacy, ChIP Chemistry Interdisciplinary Project Research Centre, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, MC, Italy.

Department of Pharmacy, University of "G. D'Annunzio" Chieti and Pescara, Via dei Vestini 1, 66100 Chieti, CH, Italy.

出版信息

Biomacromolecules. 2025 May 12;26(5):3234-3254. doi: 10.1021/acs.biomac.5c00387. Epub 2025 Apr 8.

DOI:10.1021/acs.biomac.5c00387
PMID:40198273
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12076507/
Abstract

Combinatorial cancer therapy benefits from injectable hydrogels for localized, controlled drug delivery. This study presents a thiol-ene conjugated hydrogel formed by cross-linking thiol-modified hyaluronic acid (HASH) with vinyl sulfone-modified β-cyclodextrin (CDVS). Four formulations (23Gel-16, 23Gel-33, 99Gel-16, 99Gel-33) were synthesized by varying HASH molecular weight (23 or 99 kDa) and CDVS modification (16% or 33%). Rheological analysis confirmed enhanced viscoelasticity with increasing molecular weight and modification (99Gel-33 > 99Gel-16 > 23Gel-33 > 23Gel-16). The system enabled combinatorial delivery of doxorubicin (DOX) and carvacrol (CRV), exhibiting tumor-responsive degradation and tunable release. DOX release accelerated under tumor-mimicking conditions (100% in 46 h vs 58.7% in PBS), while CRV showed an initial burst followed by sustained release. The hydrogel promoted mesenchymal stem cell proliferation and effectively inhibited triple-negative breast cancer cells. This injectable, tumor-responsive hydrogel system offers a promising platform for minimally invasive, personalized cancer therapy.

摘要

组合癌症疗法受益于可注射水凝胶用于局部、可控药物递送。本研究展示了一种通过将硫醇修饰的透明质酸（HASH）与乙烯基砜修饰的β-环糊精（CDVS）交联形成的硫醇-烯共轭水凝胶。通过改变HASH分子量（23或99 kDa）和CDVS修饰（16%或33%）合成了四种配方（23Gel-16、23Gel-33、99Gel-16、99Gel-33）。流变学分析证实，随着分子量和修饰的增加，粘弹性增强（99Gel-33 > 99Gel-16 > 23Gel-33 > 23Gel-16）。该系统能够实现阿霉素（DOX）和香芹酚（CRV）的组合递送，表现出肿瘤响应性降解和可调节释放。在模拟肿瘤条件下，DOX释放加速（46小时内释放100%，而在PBS中为58.7%），而CRV显示出初始爆发后持续释放。水凝胶促进间充质干细胞增殖并有效抑制三阴性乳腺癌细胞。这种可注射的、肿瘤响应性水凝胶系统为微创、个性化癌症治疗提供了一个有前景的平台。

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Localized Cancer Treatment Using Thiol-Ene Hydrogels for Dual Drug Delivery.

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引用本文的文献

[1]
Research Strategies and Methods of Hydrogels for Antitumor Drug Delivery.

Biomedicines. 2025-8-4

[2]
Hydrogels as advanced drug delivery platforms for cancer immunotherapy: promising innovations and future outlook.

J Nanobiotechnology. 2025-7-28

[3]
Dual-Drug Delivery Systems Using Hydrogel-Nanoparticle Composites: Recent Advances and Key Applications.

Gels. 2025-7-3

本文引用的文献

[1]
Hydrogel-based platforms for site-specific doxorubicin release in cancer therapy.

J Transl Med. 2024-9-30

[2]
Modification and crosslinking strategies for hyaluronic acid-based hydrogel biomaterials.

Smart Med. 2023-10-30

[3]
Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions.

Signal Transduct Target Ther. 2024-7-1

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A comprehensive review on doxorubicin: mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer.

Drug Deliv Transl Res. 2025-1

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Injectable bio-multifunctional hyaluronic acid-based hydrogels loaded with poly ADP-ribose polymerase inhibitors for ovarian cancer therapy.

Int J Biol Macromol. 2024-6

[6]
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Int J Mol Sci. 2024-4-21

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Multifunctionality of cyclodextrin-based polymeric nanoparticulate delivery systems for chemotherapeutics, combination therapy, and theranostics.

Int J Pharm. 2024-4-10

[8]
Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review.

Front Endocrinol (Lausanne). 2023

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Pharmaceutics. 2023-10-23

[10]
Fractional order ATR-FTIR differential spectroscopy for detection of weak bands and assessing the radiation modifications in gamma sterilized UHMWPE.

PLoS One. 2023

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