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Dendrimer-like AB 2 -type star polymers as nanocarriers for doxorubicin delivery to breast cancer cells: synthesis, characterization, in-vitro release and cytotoxicity studies
Journal of Polymer Research ( IF 2.8 ) Pub Date : 2020-07-02 , DOI: 10.1007/s10965-020-02089-2
See Kiat Wong , Ismail Zainol , Mei Peng Ng , Chew Hee Ng , Ing Hong Ooi

Novel Pentaerythritol (PTL)- and dipentaerythritol (DPTL)-cored dendrimer-like star polymers with AB2 miktoarms [A = poly(L-Lactide); poly(ethylene glycol)-folate] (1g and 2g) were synthesized and characterized by proton magnetic resonance spectroscopy, fourier transform infrared, gel permeation chromatography and differential scanning calorimetric techniques. Anticancer drug doxorubicin was encapsulated into the star polymer nanoparticles using nanoprecipitation technique. The doxorubicin-loaded nanoparticles of the star polymer with PTL core (1g-NPs-DOX) and DPTL core (2g-NPs-DOX) were spherical and had average diameters of 185.88 ± 27.53 nm and 203.66 ± 20.69 nm, and zeta potential of −19.54 ± 0.57 mV and − 14.77 ± 1.16 mV, respectively. 2g-NPs-DOX had higher doxorubicin loading and encapsulation efficiency (14.59% ± 0.001; 87.54% ± 0.003) than those of 1g-NPs-DOX (12.88% ± 0.006; 77.29% ± 0.039). In vitro release studies showed that an initial burst release of doxorubicin was followed by a sustained release over 7 days, which were significantly higher at pH 5.3 than at pH 7.4. Both drug-free nanoparticles 1g-NPs and 2g-NPs exhibited low cytotoxic effect against MCF-7 and MCF-10a with over 80% cell viability at maximum concentration (100 μM) after 72 h of incubation. Due to sustained release, the IC50 values (72 h) of 1g-NPs-DOX and 2g-NPs-DOX against MCF-7 cells were 22.5 μM and 19.5 μM respectively, as compared to 41.0 μM and 32.0 μM against MCF-10a cells, which suggested that 1g-NPs-DOX and 2g-NPs-DOX are more effective in inhibiting the breast cancer cell viability. Hence, the dendrimer-like star polymers, 1g and 2g, showed good potential as nanocarriers for preferential delivery of doxorubicin to the breast cancer cells.



中文翻译:

类树状聚合物AB 2型星形聚合物作为阿霉素递送至乳腺癌细胞的纳米载体:合成,表征,体外释放和细胞毒性研究

新型季戊四醇(PTL)和二季戊四醇(DPTL)核心的树状聚合物状星形聚合物,带有AB 2链[A =聚(L-丙交酯);通过质子磁共振波谱,傅立叶变换红外光谱,凝胶渗透色谱和差示扫描量热技术,合成并表征了聚乙二醇-叶酸(1g2g)。使用纳米沉淀技术将抗癌药阿霉素包封在星形聚合物纳米颗粒中。具有PTL核心(1g-NPs-DOX)和DPTL核心(2g-NPs-DOX)的星形聚合物的阿霉素负载纳米颗粒呈球形,平均直径分别为185.88±27.53 nm和203.66±20.69 nm,ζ电位分别为-19.54±0.57 mV和-14.77±1.16 mV。2g-NPs-DOX的阿霉素装载量和包封效率(14.59%±0.001; 87.54%±0.003)比1g-NPs-DOX(12.88%±0.006; 77.29%±0.039)高。体外释放研究表明,阿霉素的初始突释释放随后是7天的持续释放,在pH 5.3时比在pH 7.4时显着更高。孵育72小时后,无药物纳米粒子1g-NPs2g-NPs对MCF-7和MCF-10a均显示出低细胞毒性作用,最大浓度(100μM)时细胞活力超过80%。由于持续释放,IC1g-NPs-DOX2g-NPs-DOX针对MCF-7细胞的50个值(72小时)分别为22.5μM和19.5μM,而针对MCF-10a细胞则为41.0μM和32.0μM。 NPs-DOX2g-NPs-DOX在抑制乳腺癌细胞生存力方面更有效。因此,树状大分子状星形聚合物1g2g作为纳米载体表现出良好的潜力,可以将阿霉素优先递送至乳腺癌细胞。

更新日期:2020-07-02
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