Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles
| Autor: | 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. |
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| Přispěvatelé: | MIT-Harvard Center for Cancer Nanotechnology Excellence, Institute for Medical Engineering and 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Glutamate Carboxypeptidase II
Male Drug Materials science Cell Survival Polymers media_common.quotation_subject Cell Biomedical Engineering Medicine (miscellaneous) Antineoplastic Agents Bioengineering Development Pharmacology Irinotecan Article Drug Delivery Systems Cell Line Tumor LNCaP medicine Humans General Materials Science media_common Cisplatin Prostate technology industry and agriculture Prostatic Neoplasms Drug Synergism Combination chemotherapy medicine.anatomical_structure Antigens Surface Cancer cell Nanoparticles Camptothecin medicine.drug |
| Zdroj: | PMC |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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