CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel
CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel
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DOI：
10.1016/j.colsurfb.2016.03.075
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发表时间：
2016-07-01
影响因子：
5.8
通讯作者：
Khan, Wahid
中科院分区：
文献类型：
--
作者：
Muntimadugu, Eameema;Kumar, Rajendra;Khan, Wahid
这种联合治疗的主要目的是通过杀死癌细胞和癌症干细胞来彻底根除肿瘤。盐碱霉素（SLM）是针对癌症干细胞的，而紫杉醇（PTX）是用于杀死癌细胞的。在阳离子稳定剂的作用下，采用乳液溶剂扩散法制备了载药聚乳酸-羟基乙酸纳米颗粒。通过动态光散射技术和透射电子显微镜测定了纳米颗粒（小于150 nm）的尺寸。体外释放研究证实了SLM和PTX在一个月以上的缓释模式。对MCF-7细胞的细胞毒性研究揭示了纳米颗粒对药物溶液的毒性潜力。透明质酸（HA）被涂覆在靶向肿瘤干细胞上过表达的CD44受体的SLM纳米颗粒表面，它们对乳腺癌细胞显示出最高的细胞毒性，IC50最低。纳米颗粒的协同细胞毒作用也被观察到。细胞摄取研究使用FITC负载纳米颗粒进行。这些颗粒在FITC溶液中表现出更好的细胞摄取，HA涂层进一步提高了1.5倍的效果。用抗CD44人抗体对MDA-MB-231细胞进行染色，用流式细胞术对CD44（+）细胞进行计数，研究纳米颗粒与CD44的结合效率。当用HA包被的SLM纳米颗粒处理时，CD44（+）细胞计数急剧减少，表明它们对癌症干细胞的效率。透明质酸包被的SLM纳米粒子和PTX纳米粒子组合对CD44（+）细胞具有最高的细胞毒性。因此，使用常规化疗药物和肿瘤干细胞抑制剂联合治疗可能是克服肿瘤耐药细胞群引起的复发的一种有希望的方法。(C) 2016 Elsevier B.V.版权所有
This combinational therapy is mainly aimed for complete eradication of tumor by killing both cancer cells and cancer stem cells. Salinomycin (SLM) was targeted towards cancer stem cells whereas paclitaxel (PTX) was used to kill cancer cells. Drug loaded poly (lactic-co-glycolic acid) nanoparticles were prepared by emulsion solvent diffusion method using cationic stabilizer. Size of the nanoparticles (below 150 nm) was determined by dynamic light scattering technique and transmission electron microscopy. In vitro release study confirmed the sustained release pattern of SLM and PTX from nanoparticles more than a month. Cytotoxicity studies on MCF-7 cells revealed the toxicity potential of nanoparticles over drug solutions. Hyaluronic acid (HA) was coated onto the surface of SLM nanoparticles for targeting CD44 receptors over expressed on cancer stem cells and they showed the highest cytotoxicity with minimum IC50 on breast cancer cells. Synergistic cytotoxic effect was also observed with combination of nanoparticles. Cell uptake studies were carried out using FITC loaded nanoparticles. These particles showed improved cellular uptake over FITC solution and HA coating further enhanced the effect by 1.5 folds. CD44 binding efficiency of nanoparticles was studied by staining MDA-MB-231 cells with anti CD44 human antibody and CD44(+) cells were enumerated using flow cytometry. CD44(+) cell count was drastically decreased when treated with HA coated SLM nanoparticles indicating their efficiency towards cancer stem cells. Combination of HA coated SLM nanoparticles and PTX nanoparticles showed the highest cytotoxicity against CD44(+) cells. Hence combinational therapy using conventional chemotherapeutic drug and cancer stem cell inhibitor could be a promising approach in overcoming cancer recurrence due to resistant cell population. (C) 2016 Elsevier B.V. All rights reserved.