Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles
Date
2013
Authors
Valencia, P.
Pridgen, E.
Perea, B.
Gadde, S.
Sweeney, C.
Kantoff, P.
Bander, N.
Lippard, S.
Langer, R.
Karnik, R.
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Journal article
Citation
Nanomedicine, 2013; 8(5):687-698
Statement of Responsibility
Pedro M Valencia, Eric M Pridgen, Brian Perea, Suresh Gadde, Christopher Sweeney, Philip W Kantoff, Neil H Bander, Stephen J Lippard, Robert Langer, Rohit Karnik, Omid C Farokhzad
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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 & METHODS: 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.
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