| 丁家宜,胡雪梅,姜帅.脂质体复合水凝胶的制备及其对肿瘤细胞杀伤作用的研究[J].中国海洋药物,2026,(5):-. |
| 脂质体复合水凝胶的制备及其对肿瘤细胞杀伤作用的研究 |
| Preparation of liposome composite hydrogels and study on their tumor cell-killing effects |
| 投稿时间：2025-04-18 修订日期：2025-07-03 |
| DOI： |
| 中文关键词: 脂质体 壳聚糖水凝胶 葡萄糖氧化酶 顺铂 海洋药物 |
| English Keywords:liposome chitosan hydrogel glucose oxidase cisplatin marine drug |
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| 中文摘要: |
| 摘 要：目的 针对肿瘤微环境的复杂性导致的化疗效果不佳的问题，构建一种共载葡萄糖氧化酶（GOx）和顺铂（CDDP）的脂质体复合水凝胶（GSCL-Gel），以实现饥饿治疗与化疗的协同增效。方法 通过反相微乳液法合成负载GOx的二氧化硅（GS），并利用薄膜水化法制备负载CDDP的脂质体（CL）及共载GS和CDDP的脂质体（GSCL），进一步将GSCL负载到温敏型壳聚糖水凝胶（Gel）中形成GSCL-Gel。使用马尔文粒度仪、扫描电镜和流变仪表征其理化性质。采用CCK-8法和细胞活死染色法评价载体安全性和对B16F10细胞的杀伤效果。结果 GS呈均匀胶囊状结构，CL的载药量为（28.6 ± 2.8）%，包封率为（55.7± 3.6）%。负载GS与CDDP的GSCL粒径均一。Gel呈现三维多孔网状结构，在37 ℃下呈凝胶态，具有良好温敏性。体外实验结果显示，用载体材料（脂质体、SiO2和水凝胶）处理后的细胞存活率均大于80%，表明载体具有良好的生物安全性。联合治疗组（GSCL-Gel）在CDDP质量浓度为100 μg/mL时，细胞存活率降至16.5%，显著低于GS-Gel和CL-Gel组，且活死染色结果显示其诱导最多的细胞死亡，证实了饥饿治疗与化疗的协同治疗效果。结论 本研究成功构建的GSCL-Gel体系通过GS介导的葡萄糖消耗、脂质体控释递送CDDP及水凝胶缓释作用的协同机制，为肿瘤微环境治疗提供了新型策略。 |
| English Summary: |
| Abstract: Objective To address the issue of poor chemotherapy efficacy caused by the complex characteristics of the tumor microenvironment (TME), we developed a liposome composite hydrogel (GSCL-Gel) co-loaded with glucose oxidase (GOx) and cisplatin (CDDP) chemotherapy drug to achieve synergistic enhancement of starvation therapy and chemotherapy. Methods GOx-loaded silica (GS) was synthesized via reverse microemulsion method, and CDDP-loaded liposomes (CL) and GS and CDDP co-loaded liposomes (GSCL) were prepared using the thin-film hydration method. Subsequently, GSCL was then incorporated into a thermosensitive chitosan hydrogel (Gel) to form GSCL-Gel. Its physicochemical properties were characterized using dynamic light scattering, scanning electron microscopy, and rheometer. The safety of the carriers and their killing effects on B16F10 cells were evaluated using the CCK-8 assay and live-dead cell staining. Results GS exhibited a uniform capsule-like shape. The drug loading capacity of the CL was (28.6 ± 2.8)%, and the encapsulation efficiency was (55.7 ± 3.6)%. GSCL loaded with GS and CDDP had uniform particle size. Gel exhibited a three-dimensional porous network structure and formed a gel state at 37 ℃, showing good thermosensitivity. In vitro experiments showed that the cell survival rates after treatment with carrier materials (liposomes, SiO2, and Gel) were all greater than 80%, indicating good biocompatibility of the carriers. At a CDDP concentration of 100 μg/mL, the combination treatment group (GSCL-Gel) reduced the cell viability to 16.5%, which was significantly lower than GS-Gel and CL-Gel groups. Moreover, live-dead staining results showed the highest number of induced cell deaths, confirming the synergistic therapeutic effect of starvation therapy and chemotherapy. Conclusion The successfully constructed GSCL-Gel system significantly enhanced antitumor efficacy through the synergistic mechanism of GS-mediated glucose consumption, liposomal controlled release delivery of CDDP, and the sustained-release effect of the hydrogel, providing a novel combination therapeutic strategy for tumor microenvironmental therapy.
Keywords: liposome; chitosan hydrogel; glucose oxidase; cisplatin; marine drug |
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