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首页> 外文期刊>ACS applied materials & interfaces >Effect of BN Nanoparticles Loaded with Doxorubicin on Tumor Cells with Multiple Drug Resistance
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Effect of BN Nanoparticles Loaded with Doxorubicin on Tumor Cells with Multiple Drug Resistance

机译:用多种耐药性对多柔比蛋白的BN纳米粒子的影响

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摘要

Herein we study the effect of doxorubicin-loaded BN nanoparticles (DOX-BNNPs) on cell lines that differ in the multidrug resistance (MDR), namely KB-3-1 and MDR KB-8-5 cervical carcinoma lines, and K562 and MDR i-S9 leukemia lines. We aim at revealing the possible differences in the cytotoxic effect of free DOX and DOX-BNNP nanoconjugates on these types of cells. The spectrophotometric measurements have demonstrated that the maximum amount of DOX in the DOX-BNNPs is obtained after saturation in alkaline solution (pH 8.4), indicating the high efficiency of BNNPs saturation with DOX. DOX release from DOX-BNNPs is a pH-dependent and DOX is more effectively released in acid medium (pH 4.05.0). Confocal laser scanning microscopy has shown that the DOX-BNNPs are internalized by neoplastic cells using endocytic pathway and distributed in cell cytoplasm near the nucleus. The cytotoxic studies have demonstrated a higher sensitivity of the leukemia lines to DOX-BNNPs compared with the carcinoma lines: IC50(DOX-BNNPs) is 1.13, 4.68, 0.025, and 0.14 g/mL for the KB-3-1, MDR KB-8-5, K562, and MDR i-S9 cell lines, respectively. To uncover the mechanism of cytotoxic effect of nanocarriers on MDR cells, DOX distribution in both the nucleus and cytoplasm has been studied. The results indicate that the DOX-BNNP nanoconjugates significantly change the dynamics of DOX accumulation in the nuclei of both KB-3-1 and KB-8-5 cells. Unlike free DOX, the utilization of DOX-BNNPs nanoconjugates allows for maintaining a high and stable level of DOX in the nucleus of MDR KB-8-5 cells.
机译:在此,我们研究了多柔比蛋白加载的BN纳米颗粒(DOX-BNNP)对多药抗性(MDR),即KB-3-1和MDR KB-8-5宫颈癌线和K562和MDR的细胞系对细胞系不同的影响I-S9白血病线条。我们旨在揭示自由DOX和DOX-BNNP纳米缀合物对这些类型细胞的细胞毒性效应的可能差异。分光光度测量表明,在碱性溶液(pH8.4)饱和后,在饱和度之后获得DOX-BNNP中的最大DOX量,表明使用DOX的BNNPS饱和度的高效率。 Dox-BNNPS的DOX释放是pH依赖性,DOX在酸性培养基中更有效地释放(pH 4.05.0)。共聚焦激光扫描显微镜表明DOX-BNNP使用内吞径通过肿瘤细胞内化,并分布在细胞内的细胞细胞质中。与癌系相比,细胞毒性研究表明,白血病系列对DOX-BNNP的敏感性更高:IC50(DOX-BNNP)为1.13,4.68,0.025和0.14g / ml,用于KB-3-1,MDR KB -8-5,K562和MDR I-S9细胞系。为了揭示纳米载体对MDR细胞上纳米载体的细胞毒性作用的机制,研究了核和细胞质中的DOX分布。结果表明,DOX-BNNP纳米缀合物显着改变KB-3-1和KB-8-5细胞核中DOX积累的动态。与免费的DOX不同,DOX-BNNPS纳米缀合物的利用允许在MDR KB-8-5细胞核中保持高且稳定的DOX水平。

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