Abstract We have developed a new methodology to attain treatment-actuated modifications in a tumor microenvironment by utilizing synergistic activity between two potential anticancer drugs. Dual drug delivery of curcumin (CUR) and 7-ethyl-10-hydroxycamptothecin (SN38) exhibits a great anti-cancer potential, as CUR enhances the effect of SN38 treatment of human cervical cells by providing microenvironment stability. However, encapsulation of CUR and SN38 obsessed by polyethylene glycol (PEG) and poly (lactic-co-glycolic acid (PLGA)-based nanoparticles (NPs) is incompetent owing to unsuitability between the binary free CUR and SN38 moieties and the polymeric system. Now, we display that SN38 can be prepared by hydrophobic covering of the drug centers with dioleoylphosphatidic acid (DOPA). The DOPA-covered SN38 can be co-encapsulated in PEG-PLGA NPs alongside CUR to stimulate excellent anticancer property. The occurrence of the SN38 suggestively enhanced the encapsulations of CUR into PEG-PLGA NPs (CUR-SN38 NPs). Formation of the nanocomposite (CUR-SN38 NPs) was confirmed by FTIR and X-ray spectroscopic techniques. Further, the morphology of CUR NPs, SN39 NPs, and CUR-SN38 NPs and nanoparticle size was examined by transmission microscopy (TEM), respectively. Furthermore CUR-SN38 NPs induced significant apoptosis in human cervical HeLa cancer cells in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assayes such as acridine orange-ethidium bromide (AO-EB), Nuclear Staining and Annexin V-FITC). The results suggest that CUR-SN38 NPs are one of the promising nursing cares for human cervical cancer therapeutic candidates worthy of further investigations.

中文翻译：

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具有双重给药系统的协同制备的聚合物纳米粒子增强宫颈癌的护理

摘要 我们开发了一种新方法，通过利用两种潜在抗癌药物之间的协同活性在肿瘤微环境中实现治疗驱动的修饰。姜黄素 (CUR) 和 7-乙基-10-羟基喜树碱 (SN38) 的双重给药表现出巨大的抗癌潜力，因为 CUR 通过提供微环境稳定性来增强 SN38 对人宫颈细胞的治疗效果。然而，由于二元游离 CUR 和 SN38 部分与聚合物体系之间的不适用性，聚乙二醇 (PEG) 和聚 (乳酸-乙醇酸共聚物 (PLGA) 基纳米粒子 (NPs) 对 CUR 和 SN38 的封装是不合适的。现在，我们展示了 SN38 可以通过用二油酰磷脂酸 (DOPA) 疏水覆盖药物中心来制备。多巴覆盖的 SN38 可以与 CUR 一起共封装在 PEG-PLGA NPs 中，以激发优异的抗癌特性。SN38 的出现暗示着增强了 CUR 向 PEG-PLGA NPs（CUR-SN38 NPs）的封装。通过 FTIR 和 X 射线光谱技术证实了纳米复合材料 (CUR-SN38 NPs) 的形成。此外，分别通过透射显微镜 (TEM) 检查了 CUR NPs、SN39 NPs 和 CUR-SN38 NPs 的形态和纳米颗粒尺寸。此外，CUR-SN38 NPs 在体外诱导人宫颈 HeLa 癌细胞显着凋亡。通过吖啶橙-溴化乙锭(AO-EB)、核染色和Annexin V-FITC等各种生化分析证实了形态学观察和细胞凋亡。