Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system.
Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system.
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基于PEG-PLL-PLGA聚合物纳米给药系统靶向逆转肿瘤多药耐药
DOI：
10.2147/ijn.s85587
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发表时间：
2015
影响因子：
8
通讯作者：
Chen B
中科院分区：
文献类型：
--
作者：
Guo L;Zhang H;Wang F;Liu P;Wang Y;Xia G;Liu R;Li X;Yin H;Jiang H;Chen B
该研究通过表面结合的转铁蛋白（Tf）研究了多药耐药（MDR）的逆转和靶向白血病细胞的纳米颗粒（NP）在裸鼠模型中的生物分布。通过由聚乙二醇（PEG）-聚-1-赖氨酸（PLL）-聚（乳酸-共-乙醇酸）（PLGA）NP组成的外涂层保护NP中的柔红霉素（DNR）和粉防己碱（泰特）的细胞毒性货物。DNR Tet Tf-PEG-PLL-PLGA NPs注射到荷MDR白血病细胞K562/A02异种移植物的裸鼠中显示出抑制肿瘤生长，并且肿瘤组织的同时免疫组织化学分析显示靶向NPs诱导肿瘤细胞凋亡。通过实时定量聚合酶链反应和Western印迹分析，靶向肿瘤细胞显示Tf受体表达显著增加，P-糖蛋白、MDR蛋白和核因子κ B显著降低。此外，DNR的浓度在血浆、肿瘤组织和主要器官中显示增加。使用近红外荧光（NIRF）染料NIR797进行流式细胞术分析，以研究Tf作为白血病细胞靶向组的有效性，这一发现得到了荷瘤裸鼠NIRF成像的支持。总之，我们的研究表明，DNR-Tet-Tf-PEG-PLL-PLGA纳米粒提供了一种特异性和有效的手段，靶向细胞毒性药物的MDR肿瘤细胞。
The study investigated the reversal of multidrug resistance (MDR) and the biodistribution of nanoparticles (NPs) that target leukemia cells in a nude mice model via a surface-bound transferrin (Tf). The cytotoxic cargo of daunorubicin (DNR) and tetrandrine (Tet) was protected in the NPs by an outer coat composed of polyethylene glycol (PEG)-poly-l-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) NPs. Injection of DNR-Tet-Tf-PEG-PLL-PLGA NPs into nude mice bearing MDR leukemia cell K562/A02 xenografts was shown to inhibit tumor growth, and contemporaneous immunohistochemical analysis of tumor tissue showed the targeted NPs induced apoptosis in tumor cells. Targeted tumor cells exhibited a marked increase in Tf receptor expression, with noticeable decreases in P-glycoprotein, MDR protein, and nuclear factor κB, as assessed by quantitative real-time polymerase chain reaction and Western blot analysis. Moreover, the concentration of DNR was shown to increase in plasma, tumor tissue, and major organs. Flow cytometry analysis with a near-infrared fluorescent (NIRF) dye, NIR797, was used to study the effectiveness of Tf as a targeting group for leukemia cells, a finding that was supported by NIRF imaging in tumor-bearing nude mice. In summary, our studies show that DNR-Tet-Tf-PEG-PLL-PLGA NPs provide a specific and effective means to target cytotoxic drugs to MDR tumor cells.