Novel ‘reporter’ nanoparticle reveals cancer treatment effectiveness in real-time.


Being able to detect early on whether a cancer therapy is working proffers obvious benefits for therapy-outcomes whilst influencing the course of treatment and improving the quality of life for the patient. However, conventional detection methods, such as PET scans, CT and MRI, cannot usually detect whether a tumour is shrinking until a patient has received multiple cycles of therapy.  Now, a study from researchers at Brigham and Women’s Hospital (BWH) offers a new approach and a read out on the effectiveness of chemotherapy or an immunotherapy in as few as eight hours after treatment. The team state that by using a nanoparticle that delivers a drug and then fluoresces green when cancer cells begin dying, they were able to visualize whether a tumour is resistant or susceptible to a particular treatment much sooner than currently available clinical methods. The study is published in the journal Proceedings of the National Academy of Sciences.

Previous studies show that the ability to monitor the efficacy of an anticancer treatment in real-time can have a critical effect on the outcome.  Current techniques, which rely on measurements of the size or metabolic state of the tumour, are sometimes unable to detect the effectiveness of an immunotherapeutic agent as the volume of the tumour may actually increase as immune cells begin to flood in to attack the tumour.  The current study takes advantage of the fact that when cells die a particular enzyme known as caspase is activated, and develops a ‘reporter element’ that glows green in the presence of activated caspase.

The current study investigated whether they could use the reporter nanoparticles to distinguish between drug-sensitive and drug-resistant tumours. Using nanoparticles loaded with anti-cancer drugs, the group tested a common chemotherapeutic agent, paclitaxel, in a pre-clinical model of prostate cancer and, separately, an immunotherapy that targets PD-L 1 in a pre-clinical model of melanoma. Results show that in the tumours that were sensitive to paclitaxel there was a 400% increase in fluorescence compared to tumours that were not sensitive to the drug.  Data findings show that there was also saw a significant increase in the fluorescent signal in tumours treated with the anti-PD-L1 nanoparticles after five days.

Results show that reporter nanoparticles cause cells to light up the moment a cancer drug starts working, allowing researchers to determine if a cancer therapy is effective within hours of treatment.  The lab state that their long-term goal is to find a way to monitor outcomes very early so that a chemotherapy drug isn’t continually given to patients who aren’t responding to it.

The team surmise that their technique can help to directly visualize and measure the responsiveness of tumours to both chemotherapy and immunotherapy, with reporter nanoparticles providing an accurate read out of whether or not cancer cells are dying.  For the future, the researchers now plan to focus on the design of radiotracers which can be used in humans, with tests of both safety and efficacy necessary before the current technique can be translated into clinical applications.

Source: Brigham and Women’s Hospital (BWH)

 

Using reporter nanoparticles loaded with either a chemotherapy or immunotherapy, researchers could distinguish between drug-sensitive and drug-resistant tumors in a pre-clinical model of prostate cancer. Credit: Ashish Kulkarni, Brigham and Women's Hospital.

Using reporter nanoparticles loaded with either a chemotherapy or immunotherapy, researchers could distinguish between drug-sensitive and drug-resistant tumors in a pre-clinical model of prostate cancer. Credit: Ashish Kulkarni, Brigham and Women’s Hospital.

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