Gabby Brauner

Health Science, '18


Online monitoring and image-guided treatment of chemoresistant micrometastases

Mentor: Bryan Spring, PhD (Northeastern University)

Chemotherapy and surgical cancer treatments for metastatic epithelial ovarian cancer and pancreatic ductal adenocarcinoma leave behind chemoresistant micrometastases that are undetectable by traditional imaging practices and leave patients susceptible to relapses, which may lead to worse prognoses for patients. This research aims to wipe out the micrometastases causing the relapses using photomedicine. By injecting the cancer cells with a photosensitive nanoparticle, light of a specific wavelength can be applied to kill the cell with a different mechanism than traditional cancer therapies. This is a new research project that is just getting off the ground, however the principles have been shown to work in other studies. My part of the project is to use cell culture to create chemoresistant cell lines that will be injected into mice to create mouse models. These cell lines will include a standard cell line, as well as a newer cell line designed to keep the heterogeneity of human tumors. It is our goal to make these mice develop human-like tumors that can be visualized and then treated using photomedicine. The aim of this project is to make a mouse model of these chemoresistant cells that can lead to treatments for chemoresistant micromestastes in humans and better prognoses of the diseases.

Activatable photocytotoxic immunoconjugates (PICs) enable micrometastesis-imaging and tumor-targeted, activatable photoimmunotherapy (taPIT). (a) The microendoscope enters the peritoneal cavity via a catheter traversing the abdominal wall. (b) Wide-field taPIT by administering scattering media (Intralipid) to the peritoneum and near inferred laser (NIR) laser light via a cylindrically diffusing fiber-optic tip. The light dose is administered equally amongst four quadrants of the cavity. (c) In vivo anti-human cytokeratin antibody has been applied to visualize the human epithelial cancer cells. An anti-mouse CD31 antibody labels the endothelial cells. Scale bars, 100 micrometers. (d) PICs are comprised of multiple self-quenching, photocytotoxic chromophores conjugated to antibodies that target and neutralize key molecules involved in tumorigenesis (e.g., EGFR). (e&f) taPIT concept in which a targeted PIC accumulates selectively within the tumor nodules, is activated by cellular processing, inhibits molecular signaling and imparts selective cytotoxicity to neoplasms upon irradiation. Source: