Reporter nanoparticle that monitors its anticancer efficacy in real time
The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be conco...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2017
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| Online Access: | http://hdl.handle.net/1721.1/106793 |
| _version_ | 1811075452205268992 |
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| author | Sabbisetti, Venkata S. Mashelkar, Raghunath A. Kulkarni, Ashish Natarajan, Siva Rao, Poornima Goldman, Aaron Khater, Yashika Korimerla, Navya Chandrasekar, Vineethkrishna Sengupta, Shiladitya |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Sabbisetti, Venkata S. Mashelkar, Raghunath A. Kulkarni, Ashish Natarajan, Siva Rao, Poornima Goldman, Aaron Khater, Yashika Korimerla, Navya Chandrasekar, Vineethkrishna Sengupta, Shiladitya |
| author_sort | Sabbisetti, Venkata S. |
| collection | MIT |
| description | The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo. |
| first_indexed | 2024-09-23T10:06:12Z |
| format | Article |
| id | mit-1721.1/106793 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:06:12Z |
| publishDate | 2017 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1067932022-09-26T15:46:34Z Reporter nanoparticle that monitors its anticancer efficacy in real time Sabbisetti, Venkata S. Mashelkar, Raghunath A. Kulkarni, Ashish Natarajan, Siva Rao, Poornima Goldman, Aaron Khater, Yashika Korimerla, Navya Chandrasekar, Vineethkrishna Sengupta, Shiladitya Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Mechanical Engineering Kulkarni, Ashish Natarajan, Siva Rao, Poornima Goldman, Aaron Khater, Yashika Korimerla, Navya Chandrasekar, Vineethkrishna Sengupta, Shiladitya The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo. Breast Cancer Research Program (U.S.) (Collaborative Innovator Grant W81XWH- 09-1-0700) National Institutes of Health (U.S.) (Grant 1R01CA135242) United States. Department of Defense (Breakthrough Award BC132168) American Lung Association (Innovation Award LCD-259932-N) American Cancer Society (Postdoctoral Fellowship 122854-PF-12-226-01-CDD) 2017-01-30T19:57:23Z 2017-01-30T19:57:23Z 2016-04 2015-05 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/106793 Kulkarni, Ashish et al. “Reporter Nanoparticle That Monitors Its Anticancer Efficacy in Real Time.” Proceedings of the National Academy of Sciences 113.15 (2016): E2104–E2113. en_US http://dx.doi.org/10.1073/pnas.1603455113 Proceedings of the National Academy of Sciences 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 National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Sabbisetti, Venkata S. Mashelkar, Raghunath A. Kulkarni, Ashish Natarajan, Siva Rao, Poornima Goldman, Aaron Khater, Yashika Korimerla, Navya Chandrasekar, Vineethkrishna Sengupta, Shiladitya Reporter nanoparticle that monitors its anticancer efficacy in real time |
| title | Reporter nanoparticle that monitors its anticancer efficacy in real time |
| title_full | Reporter nanoparticle that monitors its anticancer efficacy in real time |
| title_fullStr | Reporter nanoparticle that monitors its anticancer efficacy in real time |
| title_full_unstemmed | Reporter nanoparticle that monitors its anticancer efficacy in real time |
| title_short | Reporter nanoparticle that monitors its anticancer efficacy in real time |
| title_sort | reporter nanoparticle that monitors its anticancer efficacy in real time |
| url | http://hdl.handle.net/1721.1/106793 |
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