| 李双,王炳杰,陶娇娇,等.基于化学动力疗法的海藻酸钠中空硫化铜载药水凝胶抗乳腺癌研究[J].中国海洋药物,2025,44(4):20-28. |
| 基于化学动力疗法的海藻酸钠中空硫化铜载药水凝胶抗乳腺癌研究 |
| Sodium alginate hollow copper sulfide drug-loading hydrogel based on chemodynamic therapy for anti-breast cancer research |
| 投稿时间：2024-03-26 修订日期：2024-05-07 |
| DOI：10.13400/j.cnki.cjmd.2025.04.001 |
| 中文关键词: 海藻酸钠 中空硫化铜 双氢青蒿素 柳氮磺吡啶 化学动力疗法 |
| English Keywords:sodium alginate hollow copper sulfide dihydroartemisinin sulfasalazine chemodynamic therapy ferroptosis |
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| 中文摘要: |
| 目的 制备一种共载双氢青蒿素(DHA)和柳氮磺吡啶(SAS)的海藻酸钠中空硫化铜(HCuS)载药水凝胶,并研究其抗肿瘤活性。方法 采用模板法制备HCuS,利用搅拌吸附法制备共载DHA和SAS的载药HCuS(DSHC),通过海藻酸钠(SA)和泊洛沙姆407(F127)物理交联包载DSHC制备可注射温敏水凝胶(DSHC-Gel)。结果 该水凝胶能响应肿瘤微环境的低pH释放铜离子(Cu2+)、DHA和SAS。Cu2+可通过类芬顿反应消耗过氧化氢(H2O2),产生活性氧(ROS)实现肿瘤化学动力学疗法(CDT)；DHA的过氧桥可被细胞内的Fe2+裂解产生ROS,缓解H2O2不足；SAS可靶向溶质载体家族7成员11(SLC7A11)来抑制谷胱甘肽(GSH)的合成。CDT联用DHA和SAS共同改善H2O2浓度不足和GSH水平过高导致的ROS生成不足问题。结果表明,DSHC-Gel在体外能显著抑制乳腺癌4T1细胞的生长。结论 通过同时缓解H2O2不足和降低GSH合成的策略为增强CDT抗肿瘤效果提供了新的思路。 |
| English Summary: |
| Objective To prepare sodium alginate hollow copper sulfide (HCuS) hydrogel loaded with dihydroartemisinin (DHA) and sulfasalazine (SAS), and to study its anti-tumor activity. Methods HCuS was prepared by template method, and drug loaded nanoparticles (DSHC) encapsulating dihydroartemisinin (DHA) and sulfasalazine (SAS) was prepared by stirring adsorption. The injectable thermosensitive hydrogel (DSHC-Gel) was prepared by physical crosslinking of sodium alginate (SA) and poloxamer 407 (F127) with DSHC. Results The hydrogel released copper ion (Cu2+), DHA and SAS under acidic tumor microenvironment. Cu2+ consumed hydrogen peroxide (H2O2) and generate reactive oxygen species (ROS) by Fenton-like reaction to achieve tumor chemodynamic therapy (CDT). DHA with peroxide bridge was cleaved by intracellular Fe2+ to generate ROS to alleviate H2O2 deficiency. SAS inhibited glutathione (GSH) synthesis by targeting solute carrier family 7 members 11 (SLC7A11). CDT combined with DHA and SAS improved low ROS generation collectively caused by H2O2 deficiency and high GSH levels. The results showed that DSHC-Gel significantly inhibited the growth of 4T1 cells in vitro. Conclusion The strategy of increasing H2O2 supply and decreasing GSH synthesis simultaneously provides a novel approach to enhance the anti-tumor effect of CDT. |
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