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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
负载富含 MicroRNA-185 的间充质干细胞来源外泌体的明胶/木质素水凝胶抑制口腔癌进展
英文原题：Gelatin/Lignin Hydrogel Loaded with Mesenchymal Stem Cell-Derived Exosomes Enriched in Microrna-185 Inhibits Progression of Oral Cancer.
查看英文原题
Gelatin/Lignin Hydrogel Loaded with Mesenchymal Stem Cell-Derived Exosomes Enriched in Microrna-185 Inhibits Progression of Oral Cancer.
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中文摘要
目的
由于口腔鳞状细胞癌（OSCC）缺乏有效的局部治疗策略，本研究旨在开发一种新型明胶/木质素水凝胶，负载富含microRNA-185的间充质干细胞（MSC）来源外泌体（miR-185 EV），用于口内递送，并系统评价其治疗效果及潜在分子机制。
材料与方法
制备明胶/木质素水凝胶并负载miR-185 EV。系统评价水凝胶的理化性质，包括微观结构、溶胀行为、化学组成和流变学特征。随后进一步评估水凝胶的稳定性、黏度、生物相容性和外泌体释放动力学。建立4-硝基喹啉-1-氧化物（4NQO）诱导的小鼠舌癌模型，通过口内给药评估水凝胶的体内抗肿瘤活性。此外，进行蛋白质组学分析以探讨miR-185 EV对OSCC的分子机制。
结果
负载miR-185 EV的明胶/木质素水凝胶表现出良好的理化性质、稳定性和生物相容性，同时延长了miR-185 EV的组织滞留时间。体内抗肿瘤疗效实验显示，负载miR-185 EV的水凝胶显著抑制肿瘤发生并减轻上皮异型增生。免疫组化分析显示水凝胶显著抑制肿瘤增殖和上皮-间质转化（EMT）。蛋白质组学分析表明，miR-185 EV通过下调白细胞介素-1（IL-1）从而抑制NF-B信号通路，抑制OSCC进展。
结论
研究结果证明成功开发了负载miR-185 EV的明胶/木质素水凝胶，该水凝胶代表了一种有效的口腔内药物递送纳米药物平台，为OSCC的临床治疗提供了一种有前景的策略。
展开英文摘要原文
Purpose: Due to the lack of effective local therapeutic strategies for oral squamous cell carcinoma (OSCC), this study aimed to develop a novel gelatin/lignin hydrogel loaded with mesenchymal stem cell (MSC)-derived exosomes enriched in microRNA-185 (miR-185 EV) for intraoral delivery, followed by systematic evaluation of its therapeutic efficacy and underlying molecular mechanisms. Materials and Methods: The gelatin/lignin hydrogel was prepared and subsequently loaded with miR-185 EV.
The physicochemical properties of the hydrogel, including microstructure, swelling behavior, chemical composition, and rheological characteristics, were systematically evaluated. Next, the stability, viscosity, biocompatibility, and exosome release kinetics of the hydrogel were further assessed. A 4-nitroquinoline-1-oxide (4NQO)-induced mouse tongue carcinogenesis model was established to assess the in vivo antitumor activity of the hydrogel via intraoral administration.
Moreover, a proteomic analysis was conducted to investigate the molecular mechanisms of miR-185 EV on OSCC. Results: The miR-185 EV-loaded gelatin/lignin hydrogel exhibited favorable physicochemical properties, stability, and biocompatibility while prolonging the tissue retention time of miR-185 EV. In vivo antitumor efficacy experiments showed that the miR-185 EV-loaded hydrogel significantly inhibited tumor occurrence and alleviated epithelial dysplasia.
Immunohistochemical analyses revealed significant suppression of tumor proliferation and epithelial-mesenchymal transition (EMT) of the hydrogel. Proteomic analysis indicated that miR-185 EV suppressed OSCC progression by downregulating interleukin-1 (IL-1 ), consequently inhibiting the NF- B signaling pathway.
Conclusion: The findings demonstrate the successful development of the miR-185 EV-loaded gelatin/lignin hydrogel that represents an effective nanomedicine platform for intraoral drug delivery, providing a promising strategy for the clinical treatment of OSCC.
论文信息
- 作者
- Liu M、Wang K、Zeng C、Jia Y、Wang J、Taledaohan A、Wang Y、Guan X
- 单位
- School of Stomatology, Capital Medical University, Beijing 100070, China.China
- 期刊
- Pharmaceutics2026 Mar 14
- 原文标识
- PubMed 41900849 · DOI 10.3390/pharmaceutics18030363
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