Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles.
Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles.
复制标题
DOI：
10.2217/nnm.12.134
复制
发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Farokhzad OC
中科院分区：
文献类型：
--
作者：
Valencia PM;Pridgen EM;Perea B;Gadde S;Sweeney C;Kantoff PW;Bander NH;Lippard SJ;Langer R;Karnik R;Farokhzad OC
伊立替康和顺铂（I&C）联合化疗的两个未探索的方面是（1）主动将两种药物靶向特定的病变细胞类型和（2）在同一载体上递送两种药物，以确保它们以明确的比例同步进入细胞。在这项工作中，我们报告了使用靶向聚合物纳米颗粒（NPs）来共同封装并将I&C递送至表达前列腺特异性膜抗原（PSMA）的癌细胞。我们通过在微流体装置内混合四种不同的前体，在一个步骤中制备靶向纳米颗粒。I&C被封装在55-nm NP中，并且与非靶向NP相比，通过PSMA表达的LNCaP细胞的内化显示出8倍的增加。共包封两种药物的NP在LNCaP细胞中表现出强烈的协同作用，组合指数为0.2。将伊立替康和顺铂共包封在靶向特定细胞类型的单个NP中的策略可能用于治疗不同类型的癌症。
Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are (1) actively targeting both drugs to a specific diseased cell type and (2) delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work we report the use of targeted polymeric nanoparticles (NPs) to co-encapsulate and deliver I&C to cancer cells expressing the Prostate Specific Membrane Antigen (PSMA). We prepared targeted NPs in a single-step by mixing four different precursors inside microfluidic devices. I&C were encapsulated in 55-nm NPs and showed an 8-fold increase in internalization by PSMA-expressing LNCaP cells compared to non-targeted NPs. NPs co-encapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2. The strategy of co-encapsulating both irinotecan and cisplatin in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer.