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Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2104-13. doi: 10.1073/pnas.1603455113. Epub 2016 Mar 29.

Reporter nanoparticle that monitors its anticancer efficacy in real time.

Author information

1
Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115; ashishk@mit.edu ram@ncl.res.in shiladit@mit.edu.
2
Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115;
3
Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
4
National Chemical Laboratory, Pune 411008, India; ashishk@mit.edu ram@ncl.res.in shiladit@mit.edu.
5
Laboratory of Nanomedicine, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115; Division of Biomedical Engineering, Harvard Medical School, Boston, MA 02115; Dana Farber Cancer Institute, Boston, MA 02115 ashishk@mit.edu ram@ncl.res.in shiladit@mit.edu.

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.

KEYWORDS:

chemotherapy; immunotherapy; monitoring; nanoparticle; reporter

PMID:
27036008
PMCID:
PMC4839457
DOI:
10.1073/pnas.1603455113
[Indexed for MEDLINE]
Free PMC Article

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