Reporter nanoparticle that monitors its anticancer efficacy in real time
Name
Kulkarni-2016-Reporter nanoparticl.pdf
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1.87 MB
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Checksum (MD5)
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Author(s)
Sabbisetti, Venkata S.
Mashelkar, Raghunath A.
Kulkarni, Ashish
Natarajan, Siva
Rao, Poornima
Goldman, Aaron
Khater, Yashika
Korimerla, Navya
Chandrasekar, Vineethkrishna
Sengupta, Shiladitya
Date Issued
April 2016
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Mechanical Engineering
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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.
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DOI of Published Version
https://doi.org/10.1073/pnas.1603455113
