Preparation And Biological Application Of Pd Hydrid Nanomedicine With Controlled Hydrogen Release

By delivering the concept of clean hydrogen energy and green catalysis to the biomedical field,engineering of hydrogen-generating nanomaterials for treatment of major diseases holds great promise.Hydrogen,as an endogenous signaling molecule with high biosafety,has been shown to be a reducing homeostatic regulator,showing a certain effect on many diseases related to inflammation and oxidative stress.However,conventional treatment methods(direct inhalation of hydrogen,injection or drinking of hydrogen-rich water)make it difficult for hydrogen molecules to reach and accumulate in deep lesion tissues efficiently due to the low solubility and diffusibility of hydrogen,which limits the therapeutic effects.How to achieve efficient storage,targeted delivery and controlled release of hydrogen is a significant scientific research for improving the therapeutic effect of hydrogen.We innovatively proposes a strategy for assisting gas therapy of nanomaterials,and solves the problems of gas therapy by virtue of the functional properties of nanomaterials.Leveraging virtue of versatile abilities of Pd hydride nanomaterials in high/stable hydrogen storage,self-catalytic hydrogenation,near-infrared(NIR)light absorption and photothermal conversion,we developed PdH nanocrystals.The specific research content mainly includes the following three parts:Firstly,we have used the cubic PdH nanocrystals for tumour-targeted and photoacoustic imaging(PAI)-guided hydrogenothermal therapy of cancer.The synthesized PdH nanocrystals have exhibited high intratumoural accumulation capability,clear NIR-controlled hydrogen release behaviours,NIR-enhanced self-catalysis bioreductivity,high NIR-photothermal effect and PAI performance.With these unique properties of PdH nanocrystals,synergetic hydrogenothermal therapy with limited systematic toxicity has been achieved by tumour-targeted delivery and PAI-guided NIR-controlled release of bioreductive hydrogen as well as generation of heat.Next,we used Pd hydride(PdH)nanoparticles for high payload of hydrogen and in situ sustained hydrogen release in Alzheimer's disease(AD)brain.By virtue of the catalytic hydrogenation effect of Pd,the released hydrogen from PdH nanoparticles exhibits high bio-reductivity in favor of effectively scavenging cytotoxic·OH in a self-catalysis way.Bio-reductive hydrogen is able to inhibit A? generation and aggregation by eliminating oxidative stress and activating the anti-oxidative pathway,consequently ameliorating the cognitive impairment in AD mice.Finally,we have used hydrogenothermal therapy for antibacterial treatment.Hydrogen has a good effect in killing bacteria,eradicating bacterial biofilm and bacterial wound healing,and further enhances its therapeutic efficacy by combination of thermal therapy.The proposed hydrogenothermal therapy provides an effective strategy for the treatment of cancer,Alzheimer's disease and bacterial infection.