dc.contributor.author | Kulkarni, Chethana | |
dc.contributor.author | Betts, Alison M. | |
dc.contributor.author | Maass, Katie F. | |
dc.contributor.author | Quadir, Mohiuddin Abdul | |
dc.contributor.author | Hammond, Paula T. | |
dc.contributor.author | Wittrup, Karl Dane | |
dc.date.accessioned | 2017-02-21T17:05:29Z | |
dc.date.available | 2017-02-21T17:05:29Z | |
dc.date.issued | 2016-01 | |
dc.date.submitted | 2015-07 | |
dc.identifier.issn | 0022-3549 | |
dc.identifier.issn | 1520-6017 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/107005 | |
dc.description.abstract | Standard cell proliferation assays use bulk media drug concentration to ascertain the potency of chemotherapeutic drugs; however, the relevant quantity is clearly the amount of drug actually taken up by the cell. To address this discrepancy, we have developed a flow cytometric clonogenic assay to correlate the amount of drug in a single cell with the cell’s ability to proliferate using a cell tracing dye and doxorubicin, a naturally fluorescent chemotherapeutic drug. By varying doxorubicin concentration in the media, length of treatment time, and treatment with verapamil, an efflux pump inhibitor, we introduced 10[superscript 5]–10[superscript 10] doxorubicin molecules per cell; then used a dye-dilution assay to simultaneously assess the number of cell divisions. We find that a cell’s ability to proliferate is a surprisingly conserved function of the number of intracellular doxorubicin molecules, resulting in single-cell IC[subscript 50] values of 4–12 million intracellular doxorubicin molecules. The developed assay is a straightforward method for understanding a drug’s single-cell potency and can be used for any fluorescent or fluorescently labeled drug, including nanoparticles or antibody–drug conjugates. | en_US |
dc.description.sponsorship | Hertz Foundation (Fellowship) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.). Graduate Research Fellowship Program | en_US |
dc.description.sponsorship | Pfizer Inc. | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Support (Core) Grant P30-CA14051) | en_US |
dc.language.iso | en_US | |
dc.publisher | Wiley Blackwell | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1002/jps.24631 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | A Flow Cytometric Clonogenic Assay Reveals the Single-Cell Potency of Doxorubicin | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Maass, Katie F. et al. “A Flow Cytometric Clonogenic Assay Reveals the Single-Cell Potency of Doxorubicin.” Journal of Pharmaceutical Sciences 104.12 (2015): 4409–4416. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Maass, Katie F. | |
dc.contributor.mitauthor | Quadir, Mohiuddin Abdul | |
dc.contributor.mitauthor | Hammond, Paula T. | |
dc.contributor.mitauthor | Wittrup, Karl Dane | |
dc.relation.journal | Journal of Pharmaceutical Sciences | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Maass, Katie F.; Kulkarni, Chethana; Quadir, Mohiuddin A.; Hammond, Paula T.; Betts, Alison M.; Wittrup, Karl Dane | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-0493-2863 | |
dc.identifier.orcid | https://orcid.org/0000-0002-5568-6455 | |
dc.identifier.orcid | https://orcid.org/0000-0003-2398-5896 | |
dspace.mitauthor.error | true | |
mit.license | OPEN_ACCESS_POLICY | en_US |