This proposal explores a new class of nanoparticles, thus, may have widespread implications in science and in patient care. Visualizing residual tumor deposits at surgery has the promise of improving patient survival for multiple tumor types, including ovarian cancer. Further, addition of phototherapy has the potential for killing tumor deposits that may be too small to see by the surgeon. Successful outcome of the proposed research activities has direct relevance towards future clinical strategies aimed at staging and treatment of ovarian cancer. At one level, targeted OVGs may be utilized in conjunction with the current standard of practice that consists of open surgical cytoreduction to identify small peritoneal lesions that cannot be identified with existing pre-operative imaging methods (e.g., CT and MRI). Identifying these lesions is detrimental to tumor relapse and patient?s survival. Furthermore, with future advancement in microendoscopy technologies, OVGs may prove useful during laparoscopic procedures aimed at staging and clinical management of ovarian cancer, particularly in high risk individuals due to family history.
Ovarian cancer ranks as the fifth most common cause of death due to cancer in women, and the leading cause of deaths from cancer of the female reproductive system. Majority of cases are diagnosed at late stage where the cancer has spread most commonly into the peritoneal cavity. Our objective under this EArly-Concept Grant for Exploratory Research (EAGER) was to investigate the transformative potential of a new type of optical nano-material for targeted intraoperative imaging of peritoneal ovarian cancers. Using genome-depleted plant infecting brome mosaic virus as a scaffold, we have engineered an optically-activated nano-construct that encapsulates indocyanine green (ICG), the only FDA-approved near infrared (NIR) dye. We refer to these constructs as optical viral ghosts (OVGs). Intellectual Merit of Our Findings: This has been a multidisciplinary collaborative effort involving virology and biophotonics capabilities at University of California, Riverside (UCR), and oncological imaging expertise at The University of Texas MD Anderson Cancer Center. Under this grant, we accomplished the following: (1) increased the fluorescence emission of OVGs by nearly 17-fold through improved formulation of the constituent materials; (2) successfully functionalized the OVGs with monoclonal antibodies to target the HER2-receptor as a biomarker of ovarian cancer; (3) demonstrated molecular targeting of the HER-2 receptor by the functionalized OVGs through flow cytometry, and fluorescence imaging of ovarian cancer cells; (4) performed in-vivo studies using ovarian cancer xenografts in mice; (5) confirmed the capability of ICG in an encapsulated formulation with targeting capability to photothermally destroy ovarian cancer cells, and the ability OVGs to elicit a photothermal response that is comparable to that of free ICG. Broader Impacts: Under this grant, we explored the physical properties of a new class of optical nanoparticles, and their potential utility in a transformative manner for ovarian cancer imaging and photo-therapy. The ability to identify and destroy all ovarian tumors will have a tremendous impact on preventing tumor recurrence, treatment success, and patient survival. Our activities provided an excellent multi-disciplinary training opportunity for students to acquire skills in virology, instrumentation, biophotonics, microscopy, and oncological imaging. Specifically, one under-represented student has been pursuing his PhD on studies related to this grant . He is expected to complete his PhD in May 2015. A female scientist, obtained her PhD in 2013. Her doctoral studies were related to the engineering of near infrared nano-structures for potential use in imaging and photothermal destruction of ovarian tumor nodules. Four PhD level scientists also worked on research activities related to this project. One female undergraduate student was also actively involved in some of the studies performed under this grant. Additionally, our research concepts, methodologies, and findings have been presented and discussed in a graduate level course, Bioengineering 227-Biophotonics I: Laser-Tissue Interactions and Therapeutics, taught at UC Riverside.
