Cancer therapies have a pernicious way of being effective only for a subset of people suffering from a particular manifestation of the disease. Because there’s no way to know whether a treatment is working until long after it has begun, patients on chemo too often suffer from a medicine that does them no good. Now researchers at Brigham and Women’s Hospital in Boston have developed a “reporter nanoparticle” that is able to ferry medication and then detect cell death around itself to notify clinicians whether the therapy it delivered is working.
Reporting in the Proceedings of the National Academy of Sciences, the researchers describe a particle that reacts to the presence of activated caspase enzyme by emitting a green fluorescence. Caspase is activated in quantity during cellular death, so a bright glow produced by the nanoparticles is indicative that nearby cells are dying. Since the nanoparticles can be made to target specific tumor cells thanks to attached antibodies, the cells that die will be predominantly cancer cells.
The team tested the technology using both the chemo drug paclitaxel, as well as the anti-PD-L1 immunotherapy agent, demonstrating that the technology works with both types of therapy.
From the study abstract:
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.
Source: Brigham and Women’s…