Platinum nanoparticles as multifunctional active nanocarriers integrating the function of high-performance antioxidant drugs

Introduction In recent years, nanomaterials that mimic natural enzymes (nanozymes) have elicited huge interest in nanomedicine (Wei and Wang, Chemical Society Reviews, 2013). In this work, we explored the use of citrate-capped... [ view full abstract ]

Introduction
In recent years, nanomaterials that mimic natural enzymes (nanozymes) have elicited huge interest in nanomedicine (Wei and Wang, Chemical Society Reviews, 2013). In this work, we explored the use of citrate-capped platinum nanoparticles (Pt NPs) as nanozymes that act simultaneously as drugs and carriers in oxidative stress-mediated diseases.

Methods
We synthesized citrate-capped Pt NPs of 5 and 20 nm of diameter and performed a systematic characterization of their superoxide dismutase (SOD)-, catalase (CAT)- and peroxidase (HRP)- like activities in cell-free environment.
As the combined function of drug and carrier requires that Pt NPs are cytocompatibles, we performed a systematic toxicity assessment (WST-1, LDH leakage, TUNEL, and DCF assay), investigating the internalization of Pt NPs and their subcellular localization by TEM and ICP-AES analyses.
Finally, to test the hypothesis that citrate-capped Pt NPs can act as a scavenging material in biological systems, we tested Pt NPs on the cellular model of a cerebrovascular disease, namely Cerebral Cavernous Malformation (CCM), characterized by an abnormal angiogenesis and associated with a significant increase in intracellular reactive oxygen species (ROS) levels.

Results and Discussion
We showed that pure, monodisperse, and endotoxin-free Pt NPs do not exert any toxicity on several cell lines, independently of the size. We proved that the absence of toxicity of Pt NPs is related to their compartmentalization and stability within the endo/lysosomal vesicles and to the absence of release of Pt ions.
We demonstrated, for the first time, that Pt nanozymes are capable to restore physiological ROS homeostasis in a real experimental model of CCM disease, founding that Pt NPs can completely recover the cellular phenotype, similar to that of wild type cells (Fig.1).
This is possible because of the strong and broad antioxidant nanozyme activity of Pt NPs, which are simultaneously endowed with strong CAT-, HRP-, and SOD-like activities, with superior performance than natural enzymes (Moglianetti et al., Nanoscale, 2016).
These findings are important and of broad interest, and open up novel perspectives in nanomedicine for the development of multifunctional active nanocarriers integrating the function of high-performance antioxidant drugs with strong potential for therapies of complex oxidative stress-related diseases.