a Medical Physics Research Center, Mashhad University of Medical Sciences , Mashhad , Iran.
b Radiation Biology Research Center , Iran University of Medical Sciences (IUMS) , Tehran , Iran.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):330-340. doi: 10.1080/21691401.2018.1557670.
A novel multifunctional nanoplatform constructed from methoxy-PEGylated poly(amidoamine) (PAMAM) generation 3 dendrimers with superparamagnetic iron oxide nanoparticles (SPIONs) entrapped in their core, containing curcumin as the payload drug and folic acid (folate) as the targeting ligand (abbreviated as FA-mPEG-PAMAM G3-CUR@SPIONs), is presented in this study. SPIONs entrapped in the core of the nanocomplex may act as a hyperthermia agent and generate localized heat upon excitation with an alternating magnetic field (AMF), thus enabling a thermo-chemotherapy strategy for cancer treatment. Accordingly, the cytotoxic effect and the mode of cell death triggered by the nanocomplex in combination with AMF were evaluated on two different cancer cell lines with various folate receptor (FR) expression levels, including KB nasopharyngeal cancer cells overexpressing FRs as the model and MCF-7 breast cancer cells with low level of FRs as the blank sample. The obtained results showed that KB cell death was greater than the cell death observed in MCF-7 cells. Moreover, a majority of cell death in both cell lines were related to apoptosis when the folate-modified nanocomplex was used instated of the non-folate-modified nanocomplex. Therefore, functionalizing the nanocomplex with folate modulated the response to thermo-chemotherapy by shifting the cell death pathways toward apoptosis.
本研究提出了一种新型多功能纳米平台,由甲氧基聚乙二醇化聚(酰胺-胺)(PAMAM)树枝状大分子与超顺磁性氧化铁纳米粒子(SPIONs)构建而成,SPIONs 被包裹在其核心内,其中包含姜黄素作为有效药物负载,叶酸(FA)作为靶向配体(缩写为 FA-mPEG-PAMAM G3-CUR@SPIONs)。纳米复合物核心内包裹的 SPIONs 可作为热疗剂,在交变磁场(AMF)激发下产生局部热量,从而实现癌症治疗的热化疗策略。因此,评估了纳米复合物与 AMF 联合使用对两种不同的具有不同叶酸受体(FR)表达水平的癌细胞系的细胞毒性作用和细胞死亡模式,包括高表达 FR 的 KB 鼻咽癌细胞作为模型和 FR 低表达的 MCF-7 乳腺癌细胞作为空白样本。结果表明,KB 细胞死亡大于 MCF-7 细胞观察到的细胞死亡。此外,当使用叶酸修饰的纳米复合物代替非叶酸修饰的纳米复合物时,两种细胞系中的大多数细胞死亡都与细胞凋亡有关。因此,通过将细胞死亡途径向细胞凋亡转移,使纳米复合物具有叶酸功能化,从而调节了对热化疗的反应。