Cyclodextrin Polymers Functionalized with Histidine and Carcinine as Chelating Therapeutics for Copper Dyshomeostasis

Abstract

In recent years, cyclodextrin polymeric nanoparticles have been designed to introduce new properties and extend their medical applications. Based on the features of cyclodextrins, we derivatized cross‐linked cyclodextrin polymers with histidine or carcinine moieties. We found that amylases do not hydrolyze cyclodextrin polymers. The new polymers can form copper(II) complexes and may act as nanochelators to counteract copper(II) dyshomeostasis‐related diseases. Furthermore, the copper(II) complexes show superoxide dismutase activity, similar to free carcinine and histidine complexes. The antioxidant biological activity of the copper(II) complex formed in situ may protect cells from oxidative damage related to copper dyshomeostasis.

Polymeric Nanozyme with SOD Activity Capable of Inhibiting Self‐ and Metal‐Induced α‐Synuclein Aggregation

“…Consequently, some of the strategies currently being pursued to address the emergence of PD rely on the development of antioxidant systems able to prevent the accumulation of ROS or to inhibit the formation of α-synuclein aggregates. [14] Considering the major role of superoxide radicals in ROS generation, [17] research on antioxidant systems has centered on the development of small ionophores whose Cu II , [18][19][20][21][22][23][24][25] Fe II , [18] Mn II , [18,26,27] and Zn II [28] complexes present superoxide dismutase (SOD) activity. Although very few such systems have yet displayed satisfactory clinical results, [29,30] the use of tetraazamacrocycles and nanotechnology are two of the emerging promising approaches to tackle neurodegenerative diseases involving oxidative stress.…”

“…Although very few such systems have yet displayed satisfactory clinical results, [29,30] the use of tetraazamacrocycles and nanotechnology are two of the emerging promising approaches to tackle neurodegenerative diseases involving oxidative stress. [20][21][22][23][24][31][32][33][34] In this context, we have recently observed that the modification of non-toxic boehmite nanoparticles (BNPs) with binuclear Cu II azamacrocycles can significantly enhance the SOD activity of such complexes. [25,31,33,35] But there is little point in eliminating ROS without disrupting the source that generates them, which are the α-synuclein peptide aggregates in the case of PD.…”

“…Considering the major role of superoxide radicals in ROS generation, [17] research on antioxidant systems has centered on the development of small ionophores whose Cu II , [18–25] Fe II , [18] Mn II , [18,26,27] and Zn II[28] complexes present superoxide dismutase (SOD) activity. Although very few such systems have yet displayed satisfactory clinical results, [29,30] the use of tetraazamacrocycles and nanotechnology are two of the emerging promising approaches to tackle neurodegenerative diseases involving oxidative stress [20–24,31–34] . In this context, we have recently observed that the modification of non‐toxic boehmite nanoparticles (BNPs) with binuclear Cu II azamacrocycles can significantly enhance the SOD activity of such complexes [25,31,33,35] .…”