Abstract

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.

Highlights

  • As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics

  • Two polymer conjugate variants were synthetized: glycogen-based conjugates modified with POx (GOX) and glycogen-based conjugates without POx (GG)

  • T1-weighted magnetic resonance (MR) signals and corresponding contrast-tonoise ratio (CNR) values were linearly dependent on concentration of Gd3+ in the conjugates (Fig. 1a,c), with the highest signal issuing from GG

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Summary

Introduction

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Glycogen is a natural hyperbranched polymer of suitable size for the EPR effect (hydrodynamic diameter ≈ 50 nm, molecular weight ≈ 10 MDa) and above the renal threshold, it is degraded into D-glucose by intracellular enzymes and further metabolized by normal physiological glycolysis[46] It is biocompatible, biodegradable[47], widely available as a natural renewable resource (oysters, plants)[48,49], and can be modified with drugs or diagnostic moieties, what makes glycogen ideally suited for use in the construction of a multimodal drug delivery system[32,46,50]

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