Abstract 635: Osteopontin Targeted Theranostic Nanomedicine for Dual-modality Imaging Guided Photodynamic Therapy for Vulnerable Atherosclerotic Plaque

Abstract

Background: Macrophage infiltration plays a vital role in vulnerable atherosclerotic plaque (VASP) progression. Our previous work has demonstrated that osteopontin (OPN), overexpressed in foamy macrophages, could be a target for VASP detection. Photodynamic therapy (PDT) can kill foamy macrophages selectively via combining photosensitizer and illumination to generate reactive oxygen species (ROS). Herein, we constructed human serum albumin (HSA)-based nanomedicine (ICG/TPZ/HSA-Ce6-OPN) to achieve precise identification of VASP by optical/MR imaging as well as specific therapy against atherosclerosis (AS). Methods: Nanomedicines (NMs) were prepared by targeting OPN peptide, conjugating MRI contrast agent Ce6-Mn 2+ , encapsulating fluorescent dye (ICG) and hypoxia-activated drug tirapazamine (TPZ) (A). Characterization, toxicity, sensitivity and therapeutic effect were evaluated in vitro . For in vivo study, ApoE –/– mice were fed with a high-fat diet and a perivascular cuff was placed around carotid artery to establish VASP model. NMs were intravenously injected to obtain optical/MR imaging signal. The size and vulnerability of plaques were evaluated after 2 weeks administration of NMs. Results: The transmission electron microscopy image (B), fluorescence (FL) spectra and UV absorption spectra manifested the discoid-shaped NMs were well-prepared (C, D). Good binding specificity were confirmed according to cellular uptake analysis. CCK-8 assay showed excellent bio-compatibility and therapeutic effect during PDT. In vivo study revealed the NMs were accumulated in VASP (F, G). Conclusion: OPN targeted NMs indicates great potentials for precise identification and therapeutic effect on AS. However, PDT is constrained by the limited light-penetration depth in tissue, so plaques in deep-seated arteries can hardly be treated. Thus, further study is required to overcome light-penetration limitation.