间充质干细胞靶向胃癌并通过隧道纳米管输送表柔比星以增强化疗效果

Yali Zhou, Yumin Li, Haibin Wang, Haolin Sun, Jing Su, Yaqiong Fan, Wei Xing, Jie Fu
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摘要

背景:表柔比星治疗胃癌效果不理想的重要原因是局部有效浓度降低。间充质干细胞对实体瘤具有靶向趋化性,并与肿瘤细胞形成隧道式纳米管,有利于各种物质的输送。本研究证明了间充质干细胞通过隧道纳米管向胃癌细胞释放表柔比星的新颖性:利用间充质干细胞向胃癌细胞释放表柔比星:使用体外Transwell迁移试验、活细胞追踪和体内靶向试验来证明间充质干细胞对胃癌的趋化性。我们使用高内容成像系统(设备类型:Operetta CLS)验证了间充质干细胞对胃癌细胞的靶向趋化性和表柔比星的负载能力。此外,还利用 Operetta CLS 观察了隧道纳米管的形成以及与胃癌细胞共培养的间充质干细胞通过间充质干细胞隧道纳米管向胃癌细胞定向释放表柔比星的情况:结果:间充质干细胞对胃癌具有靶向趋化性,能有效负载表柔比星并具有耐受性。共培养诱导这些细胞之间形成隧道纳米管。装载表柔比星的间充质干细胞通过隧道纳米管释放到胃癌细胞中,与阴性对照组相比,显著增加了胃癌细胞的不存活性(p < 0.05):我们发现了一种精确靶向胃癌细胞释放表柔比星的新方法。因此,间充质干细胞隧道纳米管可作为一种潜在的靶向给药工具,增强对癌细胞的化疗效果。
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Mesenchymal Stem Cells Target Gastric Cancer and Deliver Epirubicin via Tunneling Nanotubes for Enhanced Chemotherapy.

Background: A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes.

Objective: Epirubicin delivery to gastric cancer cells using mesenchymal stem cells.

Methods: In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS.

Results: Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05).

Conclusions: We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.

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