Mi Yu, Mu Chaofeng, Wolfram Joy, Deng Zaian, Hu Tony Ye, Liu Xuewu, Blanco Elvin, Shen Haifa, Ferrari Mauro
Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave, Houston, TX, 77030, USA.
Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.
Adv Healthc Mater. 2016 Apr 20;5(8):936-46. doi: 10.1002/adhm.201500910. Epub 2016 Feb 18.
The successful treatment of malignant disease generally requires the use of multiple therapeutic agents that are coordinated in a spatiotemporal manner to enable synergy. Here, a porous silicon-based micro/nano composite (MNC) that is capable of simultaneously delivering chemotherapeutic agents and small interfering RNA (siRNA) to the lungs following intravenous injection is designed. The pores of the silicon microparticles are loaded with B-Raf proto-oncogene serine/threonine kinase (BRAF) siRNA-containing liposomes, while the surface is conjugated with docetaxel-encapsulated polymeric nanoparticles. The synergistic antitumor effect of the MNC is demonstrated in vitro in melanoma cells and in vivo using a mouse model for melanoma lung metastasis. The MNC displays superior therapeutic efficacy and increased accumulation in metastatic melanoma lesions in the lungs in comparison to combination therapy with liposomes and polymers. The results indicate that the MNC can be used as an effective delivery vehicle for simultaneous enrichment of multiple therapeutic agents in the lungs.
恶性疾病的成功治疗通常需要使用多种治疗药物，这些药物需在时空上协同作用以实现协同效应。在此，设计了一种基于多孔硅的微/纳米复合材料（MNC），其能够在静脉注射后将化疗药物和小干扰RNA（siRNA）同时递送至肺部。硅微粒的孔隙中装载了含B-Raf原癌基因丝氨酸/苏氨酸激酶（BRAF）siRNA的脂质体，而其表面则与包裹多西他赛的聚合物纳米颗粒偶联。MNC的协同抗肿瘤作用在体外黑色素瘤细胞中以及在体内使用黑色素瘤肺转移小鼠模型得到了证实。与脂质体和聚合物联合治疗相比，MNC在肺部转移性黑色素瘤病灶中显示出卓越的治疗效果和更高的蓄积量。结果表明，MNC可作为一种有效的递送载体，用于在肺部同时富集多种治疗药物。
