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Pro-angiogenic properties of cerium oxide nanoparticles: Role of surface Ce3+/Ce4+ ratio on induction of tube formation

S. Das, S. Singh, J.M. Dowding, S. Oommen, A. Kumar, C.R. Patra, N.E. Vlahakis, D. Mukhopadhyay, W.T. Self, S. Seal
University of Central Florida, US

Keywords: Cerium oxide nanoparticle, Ce3+/Ce4+ ratio, pro-angiogenesis


CNPs have been established in recent years as a biocompatible and redox active nanomaterial due to its unique surface chemistry at the nanoparticle scale2. The redox activity of the CNPs is facilitated by the ability of CNPs to mediate its oxidation state between 3+ and 4+ oxidation states. The Ce3+/Ce4+ ratio can be tuned based upon the synthesis process. As surface properties of the CNPs are key in determining how nanoparticles interact with cells and catalyze reactions inside and outside of cells3, we aimed to determine whether the oxidation state variation (Ce3+/Ce4+ ratio) in CNPs affected the process of angiogenesis. CNPs were synthesized to vary the surface Ce3+/Ce4+ ratio without any variation in size or shape of nanoparticles, one (CNPs I) having predominantly 3+ oxidation state (~57%) and another (CNPs II) having less 3+ oxidation state (~27%). Both the CNPs having a size distribution of 3-5nm. CNP I showed very robust angiogenesis with very nice and matured vascular sprouting, however CNP II angiogenic response was not as robust as CNP I. From these results it may be concluded that the higher induction of tube formation by CNP I over CNP II may be due to higher amount of Ce3+ on the surface of the nanoparticle, making it more redox active. Therefore, we strongly believe that the pro-angiogenic properties of nanoceria, especially nanoceria with +3 oxidation state can be exploited to develop new treatment strategies for wound healing, cardiovascular and ischemic diseases in future.
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