Nanotechnology in Science and Medicine: Applications in Cancer Diagnosis, Imaging, and Treatment
Ovarian cancer is the deadliest gynecological disease and the fifth leading cause of cancer death in women. The vast majority of patients present with late-stage, peritoneally widespread disease, which is difficult to treat and rarely leads to long-term remissions. First-line therapy includes a combination of aggressive cyto-reduction surgery and platinum-based therapy, which can be initially effective. Nevertheless, more than two-thirds of late-stage patients relapse and develop increasing resistance to platinum. Consequently, a great challenge in platinum cancer therapy is the management of chemoresistant tumor cells, including cancer stem cells.
Consequently, our laboratory has a long-standing research interest to develop more effective and less toxic vehicles for therapeutic delivery by harnessing the power of nanotechnology. We are uniquely positioned and well prepared to carry out these studies, which have been part of a strong interdisciplinary collaborative effort at Harvard Medical School, Northeastern University, and MIT to develop improved “homing” technologies for the delivery of therapeutic agents specifically targeting and sensitizing platinum resistant tumor cells, including cancer stem cells, in a spatio-temporal fashion.
Our data suggest that nanoparticles significantly reduce the toxicity profile normally seen in patients treated with platinum therapy. Additionally, the efficacy of nanoparticle-based cisplatin is at least comparable and, in some cases, even greater than the most potent traditional platinum compounds, such as cisplatin, delivered intraperitoneally. The results further indicate that nanoparticles can serve as a useful tool in delivering cytotoxic “payload” drugs to the bulk of tumor cells, in addition to multiple pathway specific inhibitors. Thus, together with our collaborators we have helped develop and test multifunctional nanoparticles, which contain small molecule inhibitors targeting key signaling pathways in ovarian cancer in addition to platinum-based cytotoxic compounds. Our aim is to develop combinatorial therapies that merge key signaling inhibitors against platinum resistant disease with nanotechnology-based delivery vehicles for a more effective therapeutic intervention. The long-term goal is to harness the power of nanotechnology to develop improved “homing” technologies for the delivery of therapeutic agents specifically targeting and sensitizing chemoresistant cells, including cancer stem cells, in a spatio-temporal fashion. Additionally, we are starting to leverage nanotechnology-based tools for improved cancer imaging and diagnosis in genetic BRCA models with an increased risk for developing the disease.