Abstract 3721: MMP9 responsive molecular beacon-loaded nanovesicles for imaging and therapy for triple negative breast cancer

Abstract

Abstract African American women are disproportionately affected by triple negative breast cancer (TNBC). Combination of tumor chemotherapy and imaging in an ‘all-in-one system' provides a useful multi-modal approach in the battle against metastatic breast cancer. A promising imaging technique, time gated molecular beacon probes, is a noninvasive and painless method for detection and monitoring. Molecular beacon probe-based theranostic nanoparticles is a novel concept in next-generation medicine that combines simultaneous diagnostics and therapeutics to radically change the way we diagnose, image and treat breast cancer. In this study, we formulated pH sensitive nanovesicles containing molecular beacons specific to MMP-9 for imaging tumor microenvironment along with an anticancer drug, thereby enabling visualization of the tumor together with therapy at the tumor site. This theranostic nanosystem will provide an exciting new tool for breast cancer diagnosis and therapy. Formulation of novel pH responsive nanovesicles were carried out using DMPC and DSPE-PG-8CH. Molecular beacons specific to MMP-9, along with cabazitaxel were encapsulated within the nanovesicles. Characterization of the formulated nanovesicles along with intracellular uptake studies were carried out in breast cancer cell lines. The hydrodynamic diameters of the vesicles were measured using a dynamic light scattering (DLS) instrument (Malvern Zetasizer Nano-ZS) and found to be ~65nm. The zeta potential varied between -55 to -60 mV. Validation of molecular beacon loading in liposome and its stability were done using spectroscopy. Results indicated a molecular beacon loading of ≈29 % in the liposomes and the liposomes were stable for atleast 2 weeks. Comparison of cleavage sequence with time MB and MB-loaded liposome showed that even after 72 hours, molecular beacon released from the liposomes were able to cleave MMP-9 and elicit an effect. This unique and innovative combinatorial theranostic strategy can improve the accuracy of imaging and therapy, provide better assessment of the severity of disease and even monitor the response to drug therapy. This innovative proposal of combining an imaging technique together with delivery of anticancer drug at the tumor site will enhance their clinical potential for diagnosis and therapy in metastatic breast cancer therapy. Citation Format: Amalendu P. Ranjan, Rafal Fudala, Sunil Shah, Andrew Gdowski, Piyush Kumar, Ignacy Grycznski, Zygmunt Grycznski, Jamboor K. Vishwanatha. MMP9 responsive molecular beacon-loaded nanovesicles for imaging and therapy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3721.