Being able to detect early on whether a cancer therapy is working for a patient can influence the course of treatment and improve outcomes and quality of life. However, conventional detection methods -- such as PET scans, CT and MRI -- usually cannot detect whether a tumor is shrinking until a patient has received multiple cycles of therapy. A new technique developed in pre-clinical models by investigators at Brigham and Women's Hospital (BWH) offers a new approach and a read out on the effectiveness of chemotherapy in as few as eight hours after treatment.
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Ref: Reporter nanoparticle that monitors its anticancer efficacy in real time. Proceedings of the National Academy of Sciences (29 March 2016) | DOI: 10.1073/pnas.1603455113
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.