Partitioning of cancer therapeutics in nuclear condensates
© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical prope...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2022
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| Online Access: | https://hdl.handle.net/1721.1/135217.2 |
| _version_ | 1810977045412315136 |
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| author | Klein, Isaac A. Boija, Ann Afeyan, Lena K. Hawken, Susana Wilson Fan, Mengyang Dall'Agnese, Alessandra Oksuz, Ozgur Henninger, Jonathan E. Shrinivas, Krishna Sabari, Benjamin R. Sagi, Ido Clark, Victoria E. Platt, Jesse M. Kar, Mrityunjoy McCall, Patrick M. Zamudio, Alicia V. Manteiga, John C. Coffey, Eliot L. Li, Charles H. Hannett, Nancy M. Guo, Yang Eric Decker, Tim-Michael Lee, Tong Ihn Zhang, Tinghu Weng, Jing-Ke Taatjes, Dylan J. Chakraborty, Arup Sharp, Phillip A. Chang, Young Tae Hyman, Anthony A. Gray, Nathanael S. Young, Richard A. |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Klein, Isaac A. Boija, Ann Afeyan, Lena K. Hawken, Susana Wilson Fan, Mengyang Dall'Agnese, Alessandra Oksuz, Ozgur Henninger, Jonathan E. Shrinivas, Krishna Sabari, Benjamin R. Sagi, Ido Clark, Victoria E. Platt, Jesse M. Kar, Mrityunjoy McCall, Patrick M. Zamudio, Alicia V. Manteiga, John C. Coffey, Eliot L. Li, Charles H. Hannett, Nancy M. Guo, Yang Eric Decker, Tim-Michael Lee, Tong Ihn Zhang, Tinghu Weng, Jing-Ke Taatjes, Dylan J. Chakraborty, Arup Sharp, Phillip A. Chang, Young Tae Hyman, Anthony A. Gray, Nathanael S. Young, Richard A. |
| author_sort | Klein, Isaac A. |
| collection | MIT |
| description | © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy. |
| first_indexed | 2024-09-23T09:04:55Z |
| format | Article |
| id | mit-1721.1/135217.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:04:55Z |
| publishDate | 2022 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/135217.22024-05-21T19:07:32Z Partitioning of cancer therapeutics in nuclear condensates Klein, Isaac A. Boija, Ann Afeyan, Lena K. Hawken, Susana Wilson Fan, Mengyang Dall'Agnese, Alessandra Oksuz, Ozgur Henninger, Jonathan E. Shrinivas, Krishna Sabari, Benjamin R. Sagi, Ido Clark, Victoria E. Platt, Jesse M. Kar, Mrityunjoy McCall, Patrick M. Zamudio, Alicia V. Manteiga, John C. Coffey, Eliot L. Li, Charles H. Hannett, Nancy M. Guo, Yang Eric Decker, Tim-Michael Lee, Tong Ihn Zhang, Tinghu Weng, Jing-Ke Taatjes, Dylan J. Chakraborty, Arup Sharp, Phillip A. Chang, Young Tae Hyman, Anthony A. Gray, Nathanael S. Young, Richard A. Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Physics Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy. 2022-02-07T15:54:22Z 2021-10-27T20:22:31Z 2022-02-07T15:54:22Z 2020-06 2019-09 2021-06-08T17:52:58Z Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 https://hdl.handle.net/1721.1/135217.2 en http://dx.doi.org/10.1126/science.aaz4427 Science Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/octet-stream American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Klein, Isaac A. Boija, Ann Afeyan, Lena K. Hawken, Susana Wilson Fan, Mengyang Dall'Agnese, Alessandra Oksuz, Ozgur Henninger, Jonathan E. Shrinivas, Krishna Sabari, Benjamin R. Sagi, Ido Clark, Victoria E. Platt, Jesse M. Kar, Mrityunjoy McCall, Patrick M. Zamudio, Alicia V. Manteiga, John C. Coffey, Eliot L. Li, Charles H. Hannett, Nancy M. Guo, Yang Eric Decker, Tim-Michael Lee, Tong Ihn Zhang, Tinghu Weng, Jing-Ke Taatjes, Dylan J. Chakraborty, Arup Sharp, Phillip A. Chang, Young Tae Hyman, Anthony A. Gray, Nathanael S. Young, Richard A. Partitioning of cancer therapeutics in nuclear condensates |
| title | Partitioning of cancer therapeutics in nuclear condensates |
| title_full | Partitioning of cancer therapeutics in nuclear condensates |
| title_fullStr | Partitioning of cancer therapeutics in nuclear condensates |
| title_full_unstemmed | Partitioning of cancer therapeutics in nuclear condensates |
| title_short | Partitioning of cancer therapeutics in nuclear condensates |
| title_sort | partitioning of cancer therapeutics in nuclear condensates |
| url | https://hdl.handle.net/1721.1/135217.2 |
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