Abstract

To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T1 relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.

Highlights

  • Around 90% of cancer patients die of tumor metastasis [1]

  • We have recently developed a nanoprobe for multimodal imaging, composed of glycogen conjugated with gadolinium (Gd-DOTA) and the red fluorescent marker Dyomics-615-NHS

  • The Glycogen Nanoprobe Is Efficiently Internalized into the Metastatic Melanoma Cell Lines

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Summary

Introduction

Around 90% of cancer patients die of tumor metastasis [1]. A detailed and accurate diagnosis of cancer metastasis is necessary in the management of metastatic disease [2]. Used imaging techniques in the clinic, such as magnetic resonance imaging (MRI), computerized tomography (CT) and positron emission tomography (PET), play a critical role in diagnosis and therapy of cancer metastasis [2,3,4]. Increased attention has been given to the establishment of functional nano-scaled materials for the application of combined cancer therapy and diagnostics, named “nano-theranostics” [7,8,9]. By using such systems, multimodal imaging is able to confirm delivery of therapeutic substances to the tumors and provides a superior visualization of treatment efficacy by real-time monitoring of treatment response [10,11]. An ideal nanoscale drug delivery platform should be biodegradable and non-toxic

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