Intraoperative imaging for detection and therapy of microscopic lesions of peritoneal disease in a murine ovarian cancer model with novel SERRS nanostars
Final Report Abstract
In the Kircher lab, at Memorial Sloan Kettering Cancer Center, we develop and use nanoparticle agents for cancer imaging. We specialize at “Surface Enhanced Resonant Raman Scattering” nanoparticles, SERRS NPs in short. We have developed these nanoparticles in such a way that they are non-toxic, safe to inject, and able to target tumors. We have previously used this type of nanoparticles for imaging a variety of cancers in animal models, such as liver cancer, breast cancer, and others. These SERRS NPs have a gold core, shaped like a star, and a thin glass shell around the core, to protect and stabilize it. When we shine a laser light on these nanoparticles, they provide a very strong, unique, and distinguishable spectral signal, similar to a barcode. In this work we use two types of nanoparticles and a ratiometric algorithm, to image ovarian cancer. Ovarian cancer is the deadliest of the gynecologic cancers, with more than 12 thousand deaths per year in the US alone. Because there are no methods for early detection, patients present late, when the tumor has spread from the ovaries to other abdominal organs. The primary surgery has the highest impact on patient’s prognosis. It has been shown that a complete resection of all visible tumors leads to best patient survival. However, most patients will recur, which might be indebted to unresectable microscopic lesions after primary surgery. We solve this problem with TASERS, which is short for “Topically Applied Surfaced Enhanced Resonant Raman Ratiometric Spectroscopy”. Instead of injecting the nanoparticles into the blood, we wash the peritoneal cavity with our nanoparticle suspension. We use two distinct types of SERS nanoparticles, two “flavors”: one type targets the tumor, whereas the other one does not. We use spectral analysis methods to measure these two signals and separate them. In this way, we were able to locate microscopic metastases, that were confirmed by histological analysis. TASERS is a very fitting method for intra-operative imaging, and for endoscopy. Also, since no IV injection is needed, we envision that our nanoparticles will soon be used in the clinic, guiding the surgeon to even the smallest tumor, and helping to provide a more complete therapy for ovarian cancer. This work has been published in ACS Nano and is highlighted in the journals breakthrough research video section: https://www.youtube.com/watch?v=JUB1G9-gECc
Publications
- (2017) Folate-Targeted Surface-Enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detection of Microscopic Ovarian Cancer. ACS nano 11 (2) 1488–1497
Oseledchyk, Anton; Andreou, Chrysafis; Wall, Matthew A.; Kircher, Moritz F.
(See online at https://doi.org/10.1021/acsnano.6b06796)
