Figure 6. . Illustration of the proposed mode of action of S100A1-N-acetylglucosamine nanoparticles in cardiac myocytes.

Extracellularly applied GlcNAc nanoparticles bind to cell surface receptors such as lectins on cardiac myocytes via their N-acetylglucosamine (GlcNAc) moiety (pink diamonds) and then undergo receptor-mediated endocytosis for internalization into the cardiac myocytes. The nanoparticles are lysed in the acidic environment of the endosome, thus releasing the GlcNAc moieties and S100A1 cargo proteins. Degradation of the endosome releases GlcNAc and S100A1 protein into the cytosol where they are free to diffuse to their predicted target proteins (thin black arrows). Proposed target proteins of GlcNAc and S100A1 modulation include key Ca²⁺ handling proteins located on the SR, myofilaments and mitochodria.

L-type: L-type Ca²⁺ channel; NCX: Na⁺/Ca²⁺ exchanger; PLB: Phospholamban; RyR2: Type 2 ryanodine receptor; SERCA: Sarcoplasmic/endoplasmic Ca²⁺-ATPase.