Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles
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 a...
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| Format: | Article |
| Language: | en_US |
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Future Medicine
2015
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| Online Access: | http://hdl.handle.net/1721.1/95422 https://orcid.org/0000-0003-0588-9286 https://orcid.org/0000-0002-2693-4982 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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| author | 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. Karnik, Rohit Valencia, Pedro M. Pridgen, Eric M. |
| author2 | MIT-Harvard Center for Cancer Nanotechnology Excellence |
| author_facet | MIT-Harvard Center for Cancer Nanotechnology Excellence 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. Karnik, Rohit Valencia, Pedro M. Pridgen, Eric M. |
| author_sort | Valencia, Pedro M |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:11:27Z |
| format | Article |
| id | mit-1721.1/95422 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:11:27Z |
| publishDate | 2015 |
| publisher | Future Medicine |
| record_format | dspace |
| spelling | mit-1721.1/954222022-09-26T10:59:40Z Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles 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. Karnik, Rohit Valencia, Pedro M. Pridgen, Eric M. 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 Valencia, Pedro M. Pridgen, Eric M. Langer, Robert Lippard, Stephen J. Farokhzad, Omid C. Karnik, Rohit 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. Prostate Cancer Foundation (Nanotherapeutics Award) MIT-Harvard Center of Cancer Nanotechnology Excellence (U54-CA151884) National Science Foundation (U.S.). Graduate Research Fellowship Program American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship 2015-02-19T20:33:47Z 2015-02-19T20:33:47Z 2012-10 2012-06 Article http://purl.org/eprint/type/JournalArticle 1743-5889 1748-6963 http://hdl.handle.net/1721.1/95422 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. https://orcid.org/0000-0003-0588-9286 https://orcid.org/0000-0002-2693-4982 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.2217/nnm.12.134 Nanomedicine Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Future Medicine PMC |
| spellingShingle | 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. Karnik, Rohit Valencia, Pedro M. Pridgen, Eric M. Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles |
| title | Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles |
| title_full | Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles |
| title_fullStr | Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles |
| title_full_unstemmed | Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles |
| title_short | Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles |
| title_sort | synergistic cytotoxicity of irinotecan and cisplatin in dual drug targeted polymeric nanoparticles |
| url | http://hdl.handle.net/1721.1/95422 https://orcid.org/0000-0003-0588-9286 https://orcid.org/0000-0002-2693-4982 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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