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Synergic fabrication of combination therapy of Irinotecan and 5-Fluoro-uracil encapsulated polymeric nanoparticles for the treatment of gastric cancer therapy

机译:伊替康和5氟 - 尿嘧啶包封聚合物纳米粒子治疗胃癌治疗的协同制造

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摘要

A novel combination therapy for the treatment of gastric cancers has been established using two or more medications with a wide range of mode of actions. The effectiveness of this hybrid drug delivery mechanism involving irinotecan (SN-38) and 5-fluorouracil (5FU) was improved based on their potent anti-tumor capacity, which increased the anticancer property of gastric cells through stabilizing the tumor microenvironment. The encapsulation of SN-38 and 5FU anticancer drugs co-loaded in polyethylene glycol (PEG) and polylactide-coglycolide (PLGA) nanoparticles (NPs) are incompetent owing to the inadequacy of the dual anticancer drugs SN-38 and 5FU encapsulated in polymeric biodegradable nanoparticles. Transmission microscopy (TEM) was used to examine the morphology of SN-38@NPs, 5FU@NPs, and SN-38-5FU@NPs, and the structure and size of these nanoparticles. Furthermore, the stability of these nanoparticles was assessed using dynamic light scattering (DLS). SN-38-5FU@NPs also induced in vitro apoptosis of human gastric cells, such as NCI-N87 and SGC-791. Morphological shifts and cell death were detected using various biochemical staining, such as Calcein+/PI and Hoechst staining. Additionally, the mechanistic investigation of cell death was verified using flow cytometry in Annex V-FITC. Altogether, this dual drug delivery approach indicates that SN-38-5FU@NPs might be used as a potential tool to improve the effectiveness of gastric cancer therapy.
机译:使用两种或更多种具有各种作用模式的药物建立了一种用于治疗胃癌的新型组合疗法。基于其有效的抗肿瘤能力,改善了涉及伊替康(SN-38)和5-氟尿嘧啶(5FU)的杂种药物递送机制的有效性,这通过稳定肿瘤微环境增加了胃细胞的抗癌性能。由于双抗癌药物SN-38和5Fu在聚合物可生物降解中包封的不足,SN-38和5Fu抗癌药物的包封在聚乙二醇(PEG)和聚酰胺 - 烯糖(PLGA)纳米颗粒(NPS)中的封装是不矛盾的纳米粒子。使用传输显微镜(TEM)用于检查SN-38 @ NPS,5FU @ NPS和SN-38-5FU @ NPS的形态,以及这些纳米颗粒的结构和尺寸。此外,使用动态光散射(DLS)评估这些纳米颗粒的稳定性。 SN-38-5FU @ NPS还诱导人胃细胞的体外凋亡,例如NCI-N87和SGC-791。使用各种生物化学染色检测形态变化和细胞死亡,例如Calcein + / Pi和Hoechst染色。另外,使用附件V-FITC中的流式细胞术进行验证细胞死亡的机械研究。完全,这种双重药物递送方法表明SN-38-5FU @ NPS可能用作提高胃癌疗法效果的潜在工具。

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