Neurodegenerations are a complex pool of diseases united by a progressive loss of neuronal cells. Retinal neurodegenerations cause several visual impairment conditions worldwide, burdening the healthcare systems and lowering patients’ quality of life. Several retinal degenerations are associated with reactive oxygen species overproduction, a well-known condition that, in the long term, has a detrimental effect on the degeneration progression. While the neuronal cells loss is irreversible, several therapeutic approaches are currently used to prevent retinal degeneration, with contained and heterogeneous effects depending on both disease and patient. In addition to the preventive therapies available in clinical practice, the scientific community has investigated several therapeutic and preventative solutions, from gene therapy to dietary supplements. Nanomedicine has excellent potential for retinal degeneration prevention. Nanoparticles with ROS scavenging capability, such as gold or cerium-oxide nanoparticles, have been proven effective as neurodegeneration counteractors, leading to intensive research to find more efficient materials for nanoparticles core. Thanks to its high antioxidant activity, solubility and stability, platinum has proven to be a valuable candidate for NPs’ core. Unfortunately, due to different protocols of synthesis, stabilization and coating, platinum nanoparticles display contrasting results in both in vitro and in vivo studies. This controversy induced a slowdown around the research on their applications. In this thesis, we demonstrate that citrate capped platinum nanoparticles, produced by seeded-growth approach and stabilized with an RSA corona, are stable in physiological solution, preserve their catalytic activity, without inducing neuronal death in vitro. Furthermore, in vivo experiments enlightened a preservation effect on retinal electrophysiology, without altering the morphology or the inflammation levels in the retina. These data together suggest that PtNPs are safe to use in vivo and have the potential to be used in medicine.

Platinum nanoparticles therapeutic strategy for the prevention of oxidative stress in retinal dystrophies

CAVALLI, ALESSIO
2022-04-28

Abstract

Neurodegenerations are a complex pool of diseases united by a progressive loss of neuronal cells. Retinal neurodegenerations cause several visual impairment conditions worldwide, burdening the healthcare systems and lowering patients’ quality of life. Several retinal degenerations are associated with reactive oxygen species overproduction, a well-known condition that, in the long term, has a detrimental effect on the degeneration progression. While the neuronal cells loss is irreversible, several therapeutic approaches are currently used to prevent retinal degeneration, with contained and heterogeneous effects depending on both disease and patient. In addition to the preventive therapies available in clinical practice, the scientific community has investigated several therapeutic and preventative solutions, from gene therapy to dietary supplements. Nanomedicine has excellent potential for retinal degeneration prevention. Nanoparticles with ROS scavenging capability, such as gold or cerium-oxide nanoparticles, have been proven effective as neurodegeneration counteractors, leading to intensive research to find more efficient materials for nanoparticles core. Thanks to its high antioxidant activity, solubility and stability, platinum has proven to be a valuable candidate for NPs’ core. Unfortunately, due to different protocols of synthesis, stabilization and coating, platinum nanoparticles display contrasting results in both in vitro and in vivo studies. This controversy induced a slowdown around the research on their applications. In this thesis, we demonstrate that citrate capped platinum nanoparticles, produced by seeded-growth approach and stabilized with an RSA corona, are stable in physiological solution, preserve their catalytic activity, without inducing neuronal death in vitro. Furthermore, in vivo experiments enlightened a preservation effect on retinal electrophysiology, without altering the morphology or the inflammation levels in the retina. These data together suggest that PtNPs are safe to use in vivo and have the potential to be used in medicine.
28-apr-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1077538
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