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Recombinant lipoproteins reinforce cytotoxicity of doxorubicin to hepatocellular carcinoma

机译:重组脂蛋白增强多柔比星的细胞毒性至肝细胞癌

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Cancer nanotherapeutics are changing the landscape of tumor treatment and used to circumvent limitations of conventional chemotherapy, such as non-specificity and low bioavailability. Reconstituted high density lipoproteins (rHDL) system is one of the most promising targeting delivery systems of chemotherapeutic drugs toward tumors. Here, we developed recombined high-density lipoprotein which can be functionalized to deliver doxorubicin intracellular with a higher efficiency. The cellular viability assay showed that the rHDL/Dox nanovectors had an enhanced efficiency in inhibiting the cell viability of hepatocellular carcinoma cell lines HepG2 and SMMC-7721. FACS and confocal microscopy was used to observe the doxorubicin delivery into cancer cells. Intracellular drug accumulation analysis confirmed that treatment of rHDL/Dox nanovectors resulted in higher intracellular doxorubicin concentration to the levels exceeding that of free drug. On the premise of efficient drug delivery, rHDL/Dox nanovectors have been preliminarily demonstrated effective inducing of cytotoxic effect and cell apoptosis to both of the cell lines in vitro. Tissue distribution experiment showed that rHDL/Dox nanovectors could also deliver doxorubicin to liver effectively. So, we proposed that this lipoprotein-based strategy holds promise for a safer and more efficient delivery of chemotherapeutic agents in the treatment of hepatocellular carcinoma.
机译:癌症纳米治疗剂正在改变肿瘤治疗的景观,并用于规避常规化学疗法的限制,例如非特异性和低生物利用度。重构的高密度脂蛋白(RHDL)系统是最有前景的化学治疗药物朝向肿瘤的靶向递送系统之一。在这里,我们开发了重组的高密度脂蛋白,其可以具有更高效率的细胞内赋予多柔比星。细胞活力测定表明,RHDL / DOX纳米液体具有增强的效率,抑制肝细胞癌细胞系HepG2和SMMC-7721的细胞活力。 FACS和共聚焦显微镜用于观察多柔比星输送到癌细胞中。细胞内药物累积分析证实,RHDL / DOX纳米液的处理导致细胞内的多柔比星浓度较高到超过游离药物的水平。在高效药物递送的前提下,RHDL / DOX纳米液预先证明了在体外诱导细胞毒性效应和细胞凋亡的有效诱导。组织分布实验表明,RHDL / DOX纳米液也可以有效地将多柔比星提供给肝脏。因此,我们提出基于脂蛋白的策略在治疗肝细胞癌时,对化学治疗剂的更加安全性和更有效地提供的承担能力。

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