Abstract

Abstract PURPOSE: Surgery plays a decisive role in cancer treatment and patient prognosis is closely linked to the size of residual tumors after cytoreduction. Even with the best surgical techniques, however, palpation and visual inspection do not always permit discrimination between malignant and normal tissue types and can lead to incomplete cancer resection. It is extremely important, therefore, to improve tumor delineation during surgery and provide efficient adjuvant treatment intraoperatively, to further eliminate occult disease sites that may be left behind. Among the explored fluorescent agents, near infrared (NIR, 750 – 900 nm) fluorescent imaging agents possess advantages of deep tissue penetration and minimal tissue autofluorescence and light scattering, making them promising candidates for optical imaging guided cancer debulking surgery. Our study is aimed to develop a nanomedicine capable of maximizing selective tumor detection via fluorescence imaging and immediate phototherapy for tumor tissue eradication. METHODS: To develop an effective theranostic probe, silicon naphthalocyanine (SiNc) with strong light absorption in the NIR region was loaded into a biodegradable polymeric nanoparticle based on the amphiphilic block polymer, poly (ethylene glycol)–poly(ε–caprolactone) (PEG–PCL). Such a design has provided a possibility to control and improve fluorescence and phototherapeutic properties of the SiNc–based theranostic agent. RESULTS: As a theranostic agent, the developed SiNc polymeric nanoparticles were evaluated by DLS, TEM (around 20 nm), NIR absorbance and fluorescence spectroscopies, ROS and hyperthermia production. The safety and effectiveness of SiNc–nanoparticles as a bioimaging agent was confirm in vitro and in vivo. In addition, high photostability of SiNc–nanoparticles have been detected. The efficiency of SiNc–nanoparticles as an NIR bioimaging agent was confirmed by recording the strong fluorescence signal in the ovarian cancer tumors. The in vitro and in vivo studies demonstrated that, after efficient tumor accumulation via i.v. administration, phototherapy mediated by SiNc can efficiently destroy ovarian cancer tumors. CONCLUSIONS: We have developed a photostable NIR theranostic nanomedicine platform that provides florescence detection of subcutaneous and orthotopic tumor xenographs as well as effective phototherapy resulting in complete tumor eradication. This theranostic agent can be potentially employed concurrently for tumor delineation with real–time NIR fluorescence signal during surgery and intraoperative targeted treatment to further eliminate non–surgically removable disease sites by non–toxic phototherapy. Citation Format: Oleh Taratula, Olena Taratula, Xiaoning Li, Canan Schumann, Shay Bracha, Milan Milovancev, Adam W. G. Alani. THERANOSTIC NANOPLATFORM FOR IMAGE–GUIDED SURGERY AND INTRAOPERATIVE PHOTOTHERAPY FOR OVARIAN CANCER TREATMENT [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr DPOC-012.

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