Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection
One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society
2013
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| Online Access: | http://hdl.handle.net/1721.1/79109 https://orcid.org/0000-0001-6518-0311 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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| author | Xiao, Zeyu Levy-Nissenbaum, Etgar Alexis, Frank Luptak, Andrej Teply, Benjamin A. Chan, Juliana Maria Shi, Jinjun Digga, Elise Cheng, Judy Langer, Robert Farokhzad, Omid C. |
| author2 | MIT-Harvard Center for Cancer Nanotechnology Excellence |
| author_facet | MIT-Harvard Center for Cancer Nanotechnology Excellence Xiao, Zeyu Levy-Nissenbaum, Etgar Alexis, Frank Luptak, Andrej Teply, Benjamin A. Chan, Juliana Maria Shi, Jinjun Digga, Elise Cheng, Judy Langer, Robert Farokhzad, Omid C. |
| author_sort | Xiao, Zeyu |
| collection | MIT |
| description | One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy to isolate PCa-specific internalizing 2′-O-methyl RNA aptamers (Apts) for NP incorporation. Twelve cycles of selection and counter-selection were done to obtain a panel of internalizing Apts, which can distinguish PCa cells from nonprostate and normal prostate cells. After Apt characterization, size minimization, and conjugation of the Apts with fluorescently labeled polymeric NPs, the NP–Apt conjugates exhibit PCa specificity and enhancement in cellular uptake when compared to nontargeted NPs lacking the internalizing Apts. Furthermore, when docetaxel, a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP–Apt, a significant improvement in cytotoxicity was achieved in targeted PCa cells. Rather than isolating high-affinity Apts as reported in previous selection processes, our selection strategy was designed to enrich cancer cell-specific internalizing Apts. A similar cell-uptake selection strategy may be used to develop specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including drugs and siRNAs, into target cells. |
| first_indexed | 2024-09-23T13:20:27Z |
| format | Article |
| id | mit-1721.1/79109 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:20:27Z |
| publishDate | 2013 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/791092022-10-01T14:38:28Z Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection Xiao, Zeyu Levy-Nissenbaum, Etgar Alexis, Frank Luptak, Andrej Teply, Benjamin A. Chan, Juliana Maria Shi, Jinjun Digga, Elise Cheng, Judy Langer, Robert Farokhzad, Omid C. MIT-Harvard Center for Cancer Nanotechnology Excellence Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Xiao, Zeyu Levy-Nissenbaum, Etgar Alexis, Frank Teply, Benjamin A. Chan, Juliana Maria Shi, JinJun Cheng, Judy Langer, Robert Farokhzad, Omid C. One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy to isolate PCa-specific internalizing 2′-O-methyl RNA aptamers (Apts) for NP incorporation. Twelve cycles of selection and counter-selection were done to obtain a panel of internalizing Apts, which can distinguish PCa cells from nonprostate and normal prostate cells. After Apt characterization, size minimization, and conjugation of the Apts with fluorescently labeled polymeric NPs, the NP–Apt conjugates exhibit PCa specificity and enhancement in cellular uptake when compared to nontargeted NPs lacking the internalizing Apts. Furthermore, when docetaxel, a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP–Apt, a significant improvement in cytotoxicity was achieved in targeted PCa cells. Rather than isolating high-affinity Apts as reported in previous selection processes, our selection strategy was designed to enrich cancer cell-specific internalizing Apts. A similar cell-uptake selection strategy may be used to develop specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including drugs and siRNAs, into target cells. National Institutes of Health (U.S.) (grant CA151884) National Institutes of Health (U.S.) (grant EB003647) David H. Koch Institute for Integrative Cancer Research at MIT (Prostate Cancer Foundation Award in Nanotherapeutics) United States. Dept. of Defense (Prostate Cancer Research Program PC 051156) 2013-06-14T15:39:34Z 2013-06-14T15:39:34Z 2012-01 2011-10 Article http://purl.org/eprint/type/JournalArticle 1936-0851 1936-086X http://hdl.handle.net/1721.1/79109 Xiao, Zeyu, Etgar Levy-Nissenbaum, Frank Alexis, Andrej Lupták, Benjamin A. Teply, Juliana M. Chan, Jinjun Shi, et al. Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection. ACS Nano 6, no. 1 (January 24, 2012): 696-704. https://orcid.org/0000-0001-6518-0311 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1021/nn204165v ACS Nano Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society PMC |
| spellingShingle | Xiao, Zeyu Levy-Nissenbaum, Etgar Alexis, Frank Luptak, Andrej Teply, Benjamin A. Chan, Juliana Maria Shi, Jinjun Digga, Elise Cheng, Judy Langer, Robert Farokhzad, Omid C. Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection |
| title | Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection |
| title_full | Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection |
| title_fullStr | Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection |
| title_full_unstemmed | Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection |
| title_short | Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection |
| title_sort | engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell uptake selection |
| url | http://hdl.handle.net/1721.1/79109 https://orcid.org/0000-0001-6518-0311 https://orcid.org/0000-0002-2640-3006 https://orcid.org/0000-0003-4255-0492 |
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