Abstract POSTER-THER-1436: Image-guided and targeted therapy of advanced ovarian cancer using theranostic nanoparticles (2015)

Abstract About 80% of ovarian cancer patients are diagnosed at the advanced stage due to lack of a specific symptom for early detection. The major clinical challenges in the treatment of advanced ovarian cancer are inability of complete removal of peritoneal tumor metastases by debulking surgery, and drug resistant recurrent tumors developed in the majority of the patients. To address those clinical challenges, we have developed HER2/neu targeted magnetic iron oxide nanoparticles (IONPs) that efficiently deliver therapeutic and imaging agents into HER2 expressing ovarian cancer cells. Amphiphilic polymer coated 10 nm core size IONPs, without or with PEG modification, were conjugated with near infrared dye (NIR-830) labeled HER2 affibody or HER2 affitoxin, which is a fusing protein containing a HER2 affibody for targeting and a modified PE38 toxin as a therapeutic agent. A chemotherapy drug cisplatin, commonly used for ovarian cancer therapy, was further conjugated to carboxyl groups on the polymer coating of IONP via a coordinate bond. First, we demonstrated targeted drug delivery, and specificity and sensitivity of non-invasive tumor imaging by optical and MR imaging following intravenous (i.v.) or intraperitoneal (i.p.) delivery of the targeted theranostic IONPs in an orthotopic SKOV3 human ovarian cancer xenograft model with a high level of HER2/neu expression. Significant inhibition of the growth of primary ovarian tumor, and peritoneal and lung metastases was found after i.v. or i.p. delivery of cisplatin using 0.5 to 5 mg/Kg of cisplatin equivalent doses of HER2 affibody- or HER2 affitoxin-IONP in the tumor bearing mice once every 5 days for five injections. Furthermore, i.p. delivery of HER2 targeted theranostic IONP-cisplatin showed significantly better responses compared with i.v. delivery of the same nanoparticles. HER2 affitoxin-IONP-cisplatin treated mouse group showed enhanced anti-tumor effect compared to HER affibody-IONP-cisplatin treated mouse group. For both delivery approaches, we detected stronger tumor growth inhibitory effect on peritoneal metastatic tumors compared to the response in the primary ovarian tumors. Interestingly, we observed marked differences in the response to HER2 targeted therapy in different tumor bearing mice in the same group, and in different tumors in the same mouse. We also found that non-invasive optical imaging and MRI can be used to monitor IONP-drug delivery into tumors and to detect good responder or poor responder tumors during the treatment. Therefore, the HER2 targeted and image-guided treatment approach using theranostic IONPs has the potential for further development of a new biomarker targeted therapy for significantly improving survival of the ovarian cancer patients Citation Format: Lily Yang, Minati Satpathy, Liya Wang, Rafal Zielinski, Weiping Qian, Malgorzata Lipowska, Jacek Capala, Andrew Wang, Hui Mao. Image-guided and targeted therapy of advanced ovarian cancer using theranostic nanoparticles [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1436.