Event
PhD Dissertation Defense: Kaitlyn Moore
Friday, October 23, 2026
3:00 p.m.
AJC 4104 (4th floor conference room)
Debbie Chu
301 405 8268
dgchu@umd.edu
Title: Photoimmunoconjugate Nanoformulations for Chemoresistant Peritoneal Metastasis
Committee members:
Dr. Huang-Chiao Huang, Chair
Dr. Dana Roque
Dr. Giuliano Scarcelli
Dr. Benjamin Powers
Dr. Srinivasa Raghavan, Dean's Representative
Abstract:
Peritoneal metastasis is the spread of cancer cells from the primary tumor, most commonly ovarian or gastrointestinal, to the peritoneum and surrounding abdominal tissues. Dissemination into the peritoneal cavity is characteristic of advanced disease, with 75% of ovarian cancer patients presenting with peritoneal metastasis at diagnosis. Despite aggressive standard-of-care treatments combining cytoreductive surgery and systemic chemotherapy, prognosis for advanced-stage ovarian cancer remains poor, with a 5-year survival rate of approximately 30% for Stage IV disease. Recurrence occurs in 70–80% of advanced-stage patients, with recurrent disease often demonstrating resistance to standard chemotherapeutic regimens. A primary driver of this multidrug resistance is the overexpression of ATP-binding cassette (ABC) transporters, including P-glycoprotein (P-gp), which actively pumps chemotherapeutic agents out of cancer cells.
Photodynamic therapy (PDT) offers a promising approach to counter this transporter-mediated resistance. PDT utilizes a photosensitizer activated by laser light to generate reactive oxygen species that disrupt or damage cancer cells. PDT has been shown to overcome multidrug resistance by modulating P-gp expression and function. However, traditional PDT relies on systemic delivery of non-targeted photosensitizers, limiting its application for disseminated peritoneal disease. Photoimmunotherapy (PIT) addresses these delivery limitations by utilizing photoimmunoconjugates (PICs), photosensitizer-antibody conjugates, for tumor-selective targeting. In this work, we employ PICs and multi-agent nanoliposomal formulations to establish a locoregional PIT strategy for chemoresistant peritoneal metastasis.
The overall goal of this dissertation is to advance the clinical applicability of PIC nanoformulations and PIT approaches for locoregional cancer therapy in chemoresistant malignancies. This was achieved by 1) demonstrating PIC-PIT’s potential to overcome chemoresistance in vivo while establishing a mouse model to study dynamic shifts in heterogeneous cell populations, and 2) evaluating a multi-agent nanoliposomal formulation for the co-delivery of PICs and chemotherapeutic agents via locoregional administration. First, we demonstrated that PIC-PIT inhibits P-gp efflux function in a mouse model of chemoresistant peritoneal metastasis, yielding a 2.6-fold increase in intracellular substrate retention in harvested tumor cells. Next, we established an imageable in vivo model of ovarian peritoneal metastasis incorporating distinct fluorescent chemosensitive and chemoresistant subpopulations to enable longitudinal and endpoint analysis of tumor heterogeneity and cell population dynamics. Finally, we synthesized multi-agent nanoliposomes co-delivering surface-conjugated PICs and encapsulated irinotecan (CPT-11) chemotherapy with long-term storage stability (>1 year), and evaluated their intraperitoneal administration in vivo to characterize the pharmacokinetics and biodistribution of CPT-11 and its active (SN-38) and inactive (SN-38G) metabolites in a peritoneal metastasis mouse model.
Committee members:
Dr. Huang-Chiao Huang, Chair
Dr. Dana Roque
Dr. Giuliano Scarcelli
Dr. Benjamin Powers
Dr. Srinivasa Raghavan, Dean's Representative
Abstract:
Peritoneal metastasis is the spread of cancer cells from the primary tumor, most commonly ovarian or gastrointestinal, to the peritoneum and surrounding abdominal tissues. Dissemination into the peritoneal cavity is characteristic of advanced disease, with 75% of ovarian cancer patients presenting with peritoneal metastasis at diagnosis. Despite aggressive standard-of-care treatments combining cytoreductive surgery and systemic chemotherapy, prognosis for advanced-stage ovarian cancer remains poor, with a 5-year survival rate of approximately 30% for Stage IV disease. Recurrence occurs in 70–80% of advanced-stage patients, with recurrent disease often demonstrating resistance to standard chemotherapeutic regimens. A primary driver of this multidrug resistance is the overexpression of ATP-binding cassette (ABC) transporters, including P-glycoprotein (P-gp), which actively pumps chemotherapeutic agents out of cancer cells.
Photodynamic therapy (PDT) offers a promising approach to counter this transporter-mediated resistance. PDT utilizes a photosensitizer activated by laser light to generate reactive oxygen species that disrupt or damage cancer cells. PDT has been shown to overcome multidrug resistance by modulating P-gp expression and function. However, traditional PDT relies on systemic delivery of non-targeted photosensitizers, limiting its application for disseminated peritoneal disease. Photoimmunotherapy (PIT) addresses these delivery limitations by utilizing photoimmunoconjugates (PICs), photosensitizer-antibody conjugates, for tumor-selective targeting. In this work, we employ PICs and multi-agent nanoliposomal formulations to establish a locoregional PIT strategy for chemoresistant peritoneal metastasis.
The overall goal of this dissertation is to advance the clinical applicability of PIC nanoformulations and PIT approaches for locoregional cancer therapy in chemoresistant malignancies. This was achieved by 1) demonstrating PIC-PIT’s potential to overcome chemoresistance in vivo while establishing a mouse model to study dynamic shifts in heterogeneous cell populations, and 2) evaluating a multi-agent nanoliposomal formulation for the co-delivery of PICs and chemotherapeutic agents via locoregional administration. First, we demonstrated that PIC-PIT inhibits P-gp efflux function in a mouse model of chemoresistant peritoneal metastasis, yielding a 2.6-fold increase in intracellular substrate retention in harvested tumor cells. Next, we established an imageable in vivo model of ovarian peritoneal metastasis incorporating distinct fluorescent chemosensitive and chemoresistant subpopulations to enable longitudinal and endpoint analysis of tumor heterogeneity and cell population dynamics. Finally, we synthesized multi-agent nanoliposomes co-delivering surface-conjugated PICs and encapsulated irinotecan (CPT-11) chemotherapy with long-term storage stability (>1 year), and evaluated their intraperitoneal administration in vivo to characterize the pharmacokinetics and biodistribution of CPT-11 and its active (SN-38) and inactive (SN-38G) metabolites in a peritoneal metastasis mouse model.
