Molecular Biotechnology Laboratory, Department of Biology, Faculty of Science, Shiraz University, PO Box: 71467-13565, Shiraz 71454, Iran.
Molecular Biotechnology Laboratory, Department of Biology, Faculty of Science, Shiraz University, PO Box: 71467-13565, Shiraz 71454, Iran.
Colloids Surf B Biointerfaces. 2017 Oct 1;158:589-601. doi: 10.1016/j.colsurfb.2017.07.044. Epub 2017 Jul 18.
In present investigation, two glucose based smart tumor-targeted drug delivery systems coupled with enzyme-sensitive release strategy are introduced. Magnetic nanoparticles (FeO) were grafted with carboxymethyl chitosan (CS) and β-cyclodextrin (β-CD) as carriers. Prodigiosin (PG) was used as the model anti-tumor drug, targeting aggressive tumor cells. The morphology, properties and composition and grafting process were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed that the core crystal size of the nanoparticles synthesized were 14.2±2.1 and 9.8±1.4nm for β-CD and CS-MNPs respectively when measured using TEM; while dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm, while modification with β-CD and CS gave values of 37.48 and 65.01emucm, respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs with an encapsulation efficiency of approximately 81% for the β-CD-MNPs, and 92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and 59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha-amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3 cells, revealed that the drug loaded nanoparticles had greater efficacy on the cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded β-CD-MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on MCF-7 cells. Complementary studies by fluorescence and confocal microscopy and flow cytometry confirm specific targeting of the nanocarriers to the cancer cells. The results suggest that CS-MNPs have higher potency and are better able to target the prodigiosin toxicity effect on cancerous cells than β-CD-MNPs.
在目前的研究中，引入了两种基于葡萄糖的智能肿瘤靶向药物输送系统，结合了酶敏感释放策略。磁性纳米粒子（FeO）接枝羧甲基壳聚糖（CS）和β-环糊精（β-CD）作为载体。灵菌红素（PG）被用作模型抗肿瘤药物，靶向侵袭性肿瘤细胞。通过透射电子显微镜（TEM）、傅里叶变换红外光谱（FT-IR）、振动样品磁强计（VSM）、X 射线衍射（XRD）分析对形态、性质和组成以及接枝过程进行了表征。结果表明，通过 TEM 测量，合成的纳米粒子的核心晶体尺寸分别为β-CD 和 CS-MNPs 的 14.2±2.1nm 和 9.8±1.4nm；而动态光散射（DLS）给出的直径分别为 121.1nm 和 38.2nm。未修饰的磁性纳米粒子的饱和磁化强度（Ms）为 50.10emucm，而修饰后的β-CD 和 CS 的 Ms 值分别为 37.48 和 65.01emucm。抗癌化合物灵菌红素（PG）以约 81%的包封效率载入 NPs，β-CD-MNPs 为 92%。这相当于每 100mg MNPs 的载药量分别为 56.17 和 59.17mg。在存在水解酶α-淀粉酶和壳聚糖酶的情况下，对负载纳米载体中灵菌红素的体外释放进行测量，结果表明，孵育 1 小时后，药物释放了 58.1%和 44.6%。PG 负载纳米载体对两种癌细胞系 MCF-7 和 HepG2 以及非癌细胞系 NIH/3T3 的细胞毒性研究表明，负载药物的纳米载体对癌细胞系具有更高的疗效。游离 PG 在 MCF-7 和 HepG2 细胞上的选择性指数（SI）分别为 1.54 和 4.42。对于负载 PG 的β-CD-MNPs，SI 降低到 1.27 和 1.85，而 CS-MNPs 的 SI 则显著提高到 MCF-7 细胞上的 7.03。荧光和共聚焦显微镜以及流式细胞术的补充研究证实了纳米载体对癌细胞的特异性靶向。结果表明，CS-MNPs 具有更高的效力，并且比β-CD-MNPs 更能够靶向灵菌红素对癌细胞的毒性作用。
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