Glycogen is a unique biological polysaccharide nanoparticle with dendrimer-like structure fabricated by nature itself through a bottom-up approach. Glycogen is inherently biodegradable, nontoxic, non-immunogenic and can be functionalized with diverse surface and internal motifs for enhanced bio-functional properties. Recently, there has been growing interest in glycogen as a natural alternative to synthetic polymers and nanoparticles in a range of biomedical applications.
Herein, the engineering of glycogen nanoparticles to obtain glucose-responsive insulin-delivery platforms and nanocarriers for delivery of nucleic acids and chemotherapeutics is shown. These constructs were carefully designed to enable the efficient insulin release in diabetic mouse models, chemotherapeutics delivery into 3D tumor microtissues and intracellular delivery of nucleic acids. Super resolution and FRET microscopy techniques were used to study the intracellular and in vivo properties of glycogen-based constructs with nanoscale resolution. Our work highlights the potential of glycogen as a versatile platform for the safe delivery of therapeutics without eliciting immune cell activation and cytotoxic effects.