A Multifunctional Nanoplatform against Multidrug Resistant Cancer: Merging the Best of Targeted Chemo/Gene/Photothermal Therapy
A Multifunctional Nanoplatform against Multidrug Resistant Cancer: Merging the Best of Targeted Chemo/Gene/Photothermal Therapy
复制标题
对抗多药耐药癌症的多功能纳米平台：融合最佳靶向化疗/基因/光热疗法
DOI：
10.1002/adfm.201704135
复制
发表时间：
2017-12-01
影响因子：
19
通讯作者：
Mei, Lin
中科院分区：
文献类型：
--
作者：
Cheng, Wei;Nie, Junpeng;Mei, Lin
结合化学、基因或光热手段的协同治疗在提高癌症治疗效果方面显示出巨大的潜力。设计了基于阿霉素(DOX)门控介孔二氧化硅纳米核(MSN)、渗透性糖蛋白(P-gp)、小干扰RNA(SiRNA)和聚多巴胺(PDA)外层的肿瘤靶向纳米粒子，用于DOX的负载和叶酸修饰。多功能纳米平台巧妙地将化学(DOX)、基因(P-gp siRNA)和光热(PDA层)物质整合在一个系统中。体外实验结果表明，DOX的释放行为既是pH响应的，也是温度响应的，并且由于MSN上的pH可切割的DOX门卫，共传递的P-gp siRNA的释放也是pH依赖的。此外，由于近红外光响应性的PDA外层和叶酸的偶联，纳米粒子表现出优异的光热活性和选择性细胞靶向能力。随后，体外和体内的抗肿瘤实验都证明了多功能纳米粒子增强了抗肿瘤效果，这表明了将化疗、基因和光热治疗结合在一个系统中的协同治疗的重要性。
Synergistic therapy that combines chemo-, gene-, or photothermal means shows great potential for enhancing the therapeutic effects on cancers. Tumor-targeted nanoparticles based on a doxorubicin (DOX)-gated mesoporous silica nanocore (MSN) encapsulated with permeability glycoprotein (P-gp) small interfering RNA (siRNA) and a polydopamine (PDA) outer layer for DOX loading and folic acid decoration are designed. The multifunctional nanoplatform tactfully integrates chemo- (DOX), gene- (P-gp siRNA), and photothermal (PDA layer) substances in one system. In vitro results reveal that DOX release behaviors are both pH- and thermal-responsive and the release of co-delivered P-gp siRNA is also pH-dependent due to the pH-cleavable DOX gatekeeper on MSN. In addition, due to the near-infrared light-responsive PDA outer layer and folic acid conjugation, the nanoparticles exhibit outstanding photothermal activity and selective cell targeting ability. Subsequently, in vitro and in vivo antitumor experiments both demonstrate the enhanced antitumor efficacy of the multifunctional nanoparticles, indicating the significance of synergistic therapy combining chemo-, gene-, and photothermal treatments in one system.