Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Nanomedicine (Impact Factor: 5.82). 10/2012; DOI: 10.2217/nnm.12.134
Source: PubMed

ABSTRACT Aim: 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 & method: Targeted NPs were prepared in a single step by mixing four different precursors inside microfluidic devices. Results: 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. Conclusion: 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. Original submitted 24 February 2012; Revised submitted 21 June 2012.

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