Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Nanomedicine (Lond). 2013 May;8(5):687-98. doi: 10.2217/nnm.12.134. Epub 2012 Oct 17.
Two unexplored aspects for irinotecan and cisplatin (I&C) combination chemotherapy are: actively targeting both drugs to a specific diseased cell type, and delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work, the authors report the use of targeted polymeric nanoparticles (NPs) to coencapsulate and deliver I&C to cancer cells expressing the prostate-specific membrane antigen.
MATERIALS & METHODS: Targeted NPs were prepared in a single step by mixing four different precursors inside microfluidic devices.
I&C were encapsulated in 55-nm NPs and showed an eightfold increase in internalization by prostate-specific membrane antigen-expressing LNCaP cells compared with nontargeted NPs. NPs coencapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2.
The strategy of coencapsulating both I&C in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer.
伊立替康和顺铂（I&C）联合化疗有两个尚未探索的方面：将这两种药物主动靶向特定的病变细胞类型，以及将这两种药物装载到同一载体上，以确保它们以定义明确的比例同步进入细胞。在这项工作中，作者报告了使用靶向聚合物纳米颗粒（NPs）来共包封和递送至表达前列腺特异性膜抗原的癌细胞的伊立替康和顺铂。
通过在微流控装置中混合四种不同的前体，一步法制备靶向 NPs。
I&C 被包裹在 55nm 的 NPs 中，与非靶向 NPs 相比，表达前列腺特异性膜抗原的 LNCaP 细胞内吞的 I&C 增加了 8 倍。共包封两种药物的 NPs 在 LNCaP 细胞中表现出强烈的协同作用，组合指数为 0.2。
将这两种药物共包封在针对特定细胞类型的单一 NP 中的策略，可能被用于治疗不同类型的癌症。
