In vitro and in vivo evaluation of cerium oxide nanoparticles in respiratory syncytial virus infection

查看全文 作　　者：Akhil [1]Patel;Jessica [1]Kosanovich;Sameera [1]Sansare;Sricharani [1]Balmuri;Vinayak [1]Sant;Kerry [1,2]M.Empey;Shilpa [1,3]Sant 机构地区：[1]Department of Pharmaceutical Sciences,School of Pharmacy,University of Pittsburgh,Pittsburgh,PA,15261,USA;[2]Center for Clinical Pharmaceutical Sciences,Department of Pharmacy and Therapeutics,School of Pharmacy,Clinical and Translational Science Institute,Department of Immunology,School of Medicine,University of Pittsburgh,Pittsburgh,PA,15261,USA;[3]Department of Bioengineering,Swanson School of Engineering,McGowan Institute for Regenerative Medicine,UPMC Hillman Cancer Center,University of Pittsburgh,Pittsburgh,PA,15261,USA 出　　处：《Bioactive Materials》索引2023年第6期,共12页 基　　金：funding support from the School of Pharmacy,University of Pittsburgh(SS),Brenneman Fund,University of Pittsburgh(KME);Graduate Student Research Scholarship from the School of Pharmacy,University of Pittsburgh(AP);special BD LSRFORTESSATM funded by NIH 1S10OD011925-01(PI:Borghesi). 摘　　要：Respiratory syncytial virus(RSV)is the most common cause of viral bronchiolitis among children worldwide,yet there is no vaccine for RSV disease.This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles(CNP)to modulate reactive oxygen(ROS)and nitrogen(RNS)species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo.Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods,respectively.Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential.In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages.Specifically,cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels.Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFαand IL-12p70,while simultaneously decreasing M2 CD206 expression.Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice.Notably,cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation,avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils,which are associated with RSV-mediated inflammation.In conclusion,we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection. 关 键 词：Cerium oxide nanoparticles Reactive oxygen species Respiratory syncytial virus Macrophage phenotypes IMMUNOMODULATION Nanoparticle shape Bioactive nanoparticles