工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Efficient Liposome Loading onto Surface of Mesenchymal Stem Cells via Electrostatic Interactions for Tumor-Targeted Drug Delivery.
Efficient Liposome Loading onto Surface of Mesenchymal Stem Cells via Electrostatic Interactions for Tumor-Targeted Drug Delivery.
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间充质干细胞(MSC)具有肿瘤归巢能力,因此有望成为癌症治疗的药物递送载体。为维持MSC的活性和功能,抗癌药物优选负载在MSC表面,而不是直接导入MSC内部。
本研究采用我们此前开发的磁性阴离子脂质体/无端肽原胶原复合物,尝试将脂质体负载于MSC表面,并评估负载脂质体的MSC作为药物载体的特性。
我们观察到,在磁场作用下,大尺寸磁性阴离子脂质体/无端肽原胶原复合物通过静电相互作用大量附着于MSC;其细胞内化程度低于小尺寸复合物。
此外,与无端肽原胶原浓度较低的复合物相比,高浓度复合物的细胞内化程度更低。基于这些结果,我们成功利用大尺寸磁性阴离子脂质体与高浓度无端肽原胶原形成复合物,高效地将脂质体负载于MSC表面。所构建的负载脂质体MSC与未负载MSC具有相近的增殖速率和分化潜能。
此外,负载脂质体MSC可有效黏附于血管内皮细胞,并在体外向癌细胞条件培养基迁移、在体内向实体瘤组织迁移。这些发现提示,负载脂质体的MSC可作为有效的细胞类药物载体,实现肿瘤靶向递送。
Mesenchymal stem cells (MSCs) have a tumor-homing capacity; therefore, MSCs are a promising drug delivery carrier for cancer therapy. To maintain the viability and activity of MSCs, anti-cancer drugs are preferably loaded on the surface of MSCs, rather than directly introduced into MSCs. In this study, we attempted to load liposomes on the surface of MSCs by using the magnetic anionic liposome/atelocollagen complexes that we previously developed and assessed the characters of liposome-loaded MSCs as drug carriers.
We observed that large-sized magnetic anionic liposome/atelocollagen complexes were abundantly associated with MSCs via electrostatic interactions under a magnetic field, and its cellular internalization was lower than that of the small-sized complexes.
Moreover, the complexes with higher atelocollagen concentrations showed lower cellular internalization than the complexes with lower atelocollagen concentrations. Based on these results, we succeeded in the efficient loading of liposomes on the surface of MSCs by using large-sized magnetic anionic liposomes complexed with a high concentration of atelocollagen. The constructed liposome-loaded MSCs showed a comparable proliferation rate and differentiation potential to non-loaded MSCs.
Furthermore, the liposome-loaded MSCs efficiently adhered to vascular endothelial cells and migrated toward the conditioned medium from cancer cells in vitro and solid tumor tissue in vivo.
These findings suggest that liposome-loaded MSCs could serve as an efficient cell-based drug carrier for tumor-targeted delivery.
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