Hyperbranched polyglycerol (hPG) has been used as a multivalent scaffold to develop a series of nanocarriers capable of high-affinity encapsulation of copper (Cu). A rationally selected set of Cu-complexing motifs has been conjugated to hPG hydroxyl groups to render the constructs potentially usable as exogenous sources of Cu for addressing different pathological conditions associated with Cu-deficiency. We have utilized a newly discovered route to attach Cu-binding domains exclusively within a hPG core by selective differentiation between the primary and secondary hydroxyl groups of the polyol. These hPG-derivatives were found to form a stable complex with Cu ions depending on the type of immobilized ligands and corresponding degree of functionalization. In addition, these Cu-bearing nano-complexes demonstrated moderately cationic surface charge resulting in adjustable protein-binding characteristics and low cellular toxicity profile. We envision that these Cu-loaded hPG nanocarriers can be used as a stable platform to transport the metal ion across the systemic circulation to supply bioavailable quantity of Cu in disease-afflicted tissues.
