Wang Kaiyuan, Yao Hui, Meng Ying, Wang Yi, Yan Xueying, Huang Rongqin
School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, China.
Acta Biomater. 2015 Apr;16:196-205. doi: 10.1016/j.actbio.2015.01.002. Epub 2015 Jan 14.
Tumor-specific therapeutic platforms designed for combined tumor therapy has recently received wide attention. In this work, a new HB5 aptamer-functionalized mesoporous silica-carbon based doxorubicin (DOX)-loaded system (MSCN-PEG-HB5/DOX) was successfully constructed and characterized for chemo-photothermal combined therapy of human epithelial growth factor receptor 2 (HER2)-positive breast cancer cells. The in vitro release result showed that MSCN-PEG-HB5/DOX exhibited pH-sensitive and NIR-triggered release manner. HB5-modified nanoparticles showed significant higher cellular uptake in HER2-positive breast cancer cells (SK-BR-3) but not in normal breast epithelial cells (MCF-10A), compared to unmodified counterparts. The intracellular uptake of functional nanoparticles was mainly based on the receptor-mediated mechanism which was energy-dependent. Cytotoxicity experiments demonstrated that combined therapy induced highest cell killing effect compared to chemotherapy and photothermal therapy alone. The combination index (CI) was 0.253 indicating the synergistic effect of chemotherapy and photothermal therapy. These findings suggested that MSCN-PEG-HB5/DOX was a potential chemo-photothermal therapeutic platform targeting to HER2-positive breast cancers.
为联合肿瘤治疗设计的肿瘤特异性治疗平台最近受到了广泛关注。在这项工作中,成功构建了一种新的HB5适配体功能化的介孔二氧化硅-碳基负载阿霉素(DOX)系统(MSCN-PEG-HB5/DOX),并对其用于人表皮生长因子受体2(HER2)阳性乳腺癌细胞的化学-光热联合治疗进行了表征。体外释放结果表明,MSCN-PEG-HB5/DOX呈现pH敏感和近红外触发的释放方式。与未修饰的对应物相比,HB5修饰的纳米颗粒在HER2阳性乳腺癌细胞(SK-BR-3)中显示出显著更高的细胞摄取,但在正常乳腺上皮细胞(MCF-10A)中则不然。功能性纳米颗粒的细胞内摄取主要基于能量依赖的受体介导机制。细胞毒性实验表明,与单独的化疗和光热疗法相比,联合治疗诱导的细胞杀伤效果最高。联合指数(CI)为0.253,表明化疗和光热疗法具有协同作用。这些发现表明,MSCN-PEG-HB5/DOX是一种针对HER2阳性乳腺癌的潜在化学-光热治疗平台。