Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles
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Lippard_Synergistic cytotoxicity.pdf
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Author(s)
Valencia, Pedro M
Pridgen, Eric M
Perea, Brian
Gadde, Suresh
Sweeney, Christopher
Kantoff, Philip W.
Bander, Neil H.
Langer, Robert
Lippard, Stephen J.
Farokhzad, Omid C.
Date Issued
October 2012
Journal
Nanomedicine
Publisher
Future Medicine
Citation
Valencia, Pedro M, Eric M Pridgen, Brian Perea, Suresh Gadde, Christopher Sweeney, Philip W Kantoff, Neil H Bander, et al. “Synergistic Cytotoxicity of Irinotecan and Cisplatin in Dual-Drug Targeted Polymeric Nanoparticles.” Nanomedicine 8, no. 5 (May 2013): 687–698.
Version
Author's final manuscript
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.
MIT Department
MIT-Harvard Center for Cancer Nanotechnology Excellence
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Mechanical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.2217/nnm.12.134
