Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence

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 tumourbearing 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. The majority of anticancer drugs are highly toxic and adversely affect healthy cells due to a lack of specific targeting 1,2. Therefore, a safe drug delivery system capable of accumulating and providing controlled drug release at the tumour site is highly desirable. Nanoparticles represent a versatile carrier for drug delivery due to their ability to passively accumulate in solid tumours. This occurs via the enhanced permeability and retention (EPR) effect, a relatively universal phenomenon whereby nano-sized structures (up to approx. 200 nm in size) become entrapped in tumour tissue due to either leaky endothelia or aberrant tumour vessel architecture. Restricted or even completely absent lymphatic drainage in tumours limits the release and passive accumulation of compounds 3. Nanotherapeutic carrier can accumulate in tumours via the EPR effect without any targeting ligand 4-6. Their size above the renal threshold (molecular weight > ca 45 kDa/hydrodynamic diameter > 8 nm) leads to prolonged circulation in the bloodstream increasing the probability of accumulation at the target site 3. Importantly, polymers can control the release of drugs, being composed of a structure responsive to external stimuli, such as pH changes in acidic cancer-cell environments 7 , the presence of enzymes, and redox potential 8,9. Thus to minimise the drug release in the bloodstream and the cytotoxic effect on healthy cells 10-12. One limitation of nanoparticles is that they tend to opsonise, clearing quickly through the reticuloendothelial system in the liver and spleen 13. However, this can be mitigated by surface modification: for instance, grafting nanoparticles with poly(ethylene oxide) (PEO) (known also as poly(ethylene glycol)-PEG) is a well-established pr...

Biodegradable Polymeric Nanoparticles for Drug Delivery to Solid Tumors

“…Natural biopolymers include animal- or plant-derived proteins and polysaccharides as well as polymers obtained from microbial sources. These are widely used in drug delivery research due to their unique properties such as abundance in nature, biodegradability, biocompatibility, and low toxicity ( Eroglu et al, 2017 ; Gálisová et al, 2020 ). However, they can be immunogenic and often require chemical modification before being used for the development of nanoparticles ( Karlsson et al, 2018 ).…”

Polymer-Based Nanosystems—A Versatile Delivery Approach

“…Other natural polymers that have attracted research interest for delivery purposes include, but are not limited to, glycogen [114][115][116], starch [114,[117][118][119][120], lignin [121,122], heparin [123,124], lentinan [14,125,126], and chondroitin sulfate [127][128][129].…”

The Advantages of Polymeric Hydrogels in Calcineurin Inhibitor Delivery

“…In particular, hydrogels have aroused great interest in biomedicine, mainly focusing on the development of scaffolds that release therapeutic agents [73][74][75][76]. In this context, hydrogels based on natural polymers have been extensively studied for applications in biomedicine due to their intrinsic characteristics of biocompatibility, biodegradability, and similarities to the extracellular matrix [45,[77][78][79]. The physicochemical characteristics of biopolymeric hydrogels used in drug delivery systems, namely molecular weight, solubility, morphology, hydrophilicity, hydrophobicity, loading and release efficiency of the drug, surface energy, gelation process, etc., have been investigated [80][81][82].…”