| With the development of science and technology,including computer technology and microscopy,nanomaterials have been discovered.It is used to describe materials between 1-100 nm within one-dimensional.Nanomaterial has unique properties which are different with bulk materials such as adjustable electronic and optical properties,excellent mechanical properties,etc.These unique properties allow a wide range of applications of nanoparticles,such as industrial production,living supplement,electronic products,nano medicine and other fields.Especially in the field of nanomedicine,nanomaterials have potential application value.Nanomaterials are the key to nanomedicine.At present,there are many kinds of nanomaterials,such as liposomes,different polymer nanostructures,protein structure,DNA nanoparticles,carbon materials,as well as inorganic nanomaterials such as mesoporous silica(MSNP),super paramagnetic iron oxide nanomaterials(SPIONs),quantum dots(QDs),gold nanoparticles(AuNPs).Because of different properties of nanomaterials,they can be applied to different aspects of the medical field including contrast agent,drug delivery,and photothermal treatment.The development of nanoparticles(NPs)for a wide range of biomedical applications promises safer and more effective solutions to numerous medical issues.When nanoparticles interact with the body in different ways,their beneficial or harmful effects will eventually result in interactions between nanoparticles with cells or subcellular.Nanoparticles can regulate the fate of cells,induce or prevent mutations,initiate cell communication,and regulate cellular functions.For many nanomaterials,interacting with cells in or outside is the way of nano-bio interactions.And the following biological effects are also important for nano-bio interactions.Cells uptake and other nano-bio interactions can be effectted by many factors such as biological environment and the physicochemical properties of nanomaterials(shape,size,surface chemistry and core materials).Besides surface chemistry modulation,changes in nanoparticle size and shape can also modulate internalization of nanoparticles and cell fate.However,a long-standing issue is whether nanoparticles with different core materials,yet identical size,shape,and surface chemistry behave similarly,i.e.whether cells are enabled with face recognition function?Moreover,when many factors exist simultaneously,which one plays a major role is is still not fully understood.To solve this dilemma,we developed a systematic approach by combining nanoparticle libraries and more comprehensive investigations on nanoparticle-cell interactions.We first synthesized a comprehensive gold nanoparticle(GNP)library containing 36 members with systematic changes in core material(Au,Pt,Pd),size(6 and 26 nm),and surface chemistry by keeping other parameters constant.The various cellular responses to these sophisticated nanoparticle modifications would reveal the answers to above questions.By studying the physicochemical properties of nanoparticles,we found that nanoparticles of different metal cores or nanoparticles of the same material with diverse ligand coatings behaved as they were identical in terms of physical appearance,solution aggregation behavior,electrostatic electrodynamic,and their interactions with surrounding bio-molecules.By investigating the cell uptake of nanoparticles,we found that PdNPs or AuNPs were internalized higher than PtNPs by comparing nanoparticles with identical surface ligands and coverage percentage.Nanoparticle size affected only the extent of cell internalization.Smaller particles possessed larger surface-to-volume ratio and,therefore,showed more effects on surface-directed nano-bio interactions.Cells internalized nanoparticles according to surface chemistry(hydrophobicity).Cell's "face regulation" function,at least for AuNPs and PdNPs,was demonstrated by a linear correlation of nano-hydrophobicity and amounts of nanoparticles internalized.Although PdNPs and AuNPs exhibited similar hydrophobicity(logP values),PtNPs were more hydrophilic for nanoparticles with the same surface chemistry.These results revealed a superior capability of human cells to differentiate foreign particles not just by their surface,but also by the physical property of their cores.Internalization by cells or even binding to cells surface may increase the cellular level of oxidative stress.To investigate such effects,we next examined cellular oxidative stress induced by libraries of PtNPs,AuNPs and PdNPs.Comparing nanoparticles with identical surface coatings,Au nanoparticles induced about 2 fold higher cellular oxidative stress than Pt and Pd nanoparticles.Within each of AuNP or PdNP library members,cellular oxidative stress induction level was correlated linearly with the cell uptake of these nanoparticles even though with different slopes.Based on this correlation,it was likely that Pt nanoparticles caused much less oxidative stress because of their capability to avoid being internalized.However,a question remained why Pd nanoparticles,which were internalized more than Au nanoparticles,caused much less cellular oxidative stress.To solve this dilemma,we next compared the ability of AuNPs and PdNPs to reduce cellular oxidative stress that was induced by nanoparticle internalization.PdNPs had a much stronger H2O2 reduction activity compare to AuNPs.Such reductive activities might significantly influence cell homeostasis because both AuNPs and PdNPs were heavily internalized by cells.Although internalization of PdNPs was higher than AuNPs,AuNPs was more toxic than PdNPs.The higher cytotoxicity of AuNPs was very likely due to the higher cellular oxidative stress they induced.They exhibited different cytotoxicity due to the different H2O2 reduction activity originated from the nanoparticle core.Here we provide an initial answer to this long-standing question utilizing a combinatorial library of nanoparticles with systematically changes in nanoparticle core material,size,and surface chemistry.Here we reveal critical effects of nanoparticle core materials on the biological activities of nanoparticles.Furthermore,such effects are likely transduced across surface small molecules and protein corona.These findings will assist nanomedicine design in diversifying functional nano carriers that label cells without internalization,that enter cells delivering therapeutical cargos without cytotoxicity,and that enter cancer cells delivering drugs and inducing toxicity simultaneously.Air pollution worldwide,especially in China and India,has caused serious health issues.Because PM2.5 particles consist of solid particles of diverse properties with payloads of inorganic,organic and biological pollutants,it is still not known what the major toxic components are and how these components induce toxicities.To explore this complex issue,we apply reductionism principle and an ultrafine particle library approach in this work.From investigation of 63 diversely functionalized ultrafine particles(FUPs)with adsorbed key pollutants.We found that FUPs have the similar size,shape,DLS and electrostatic and electrodynamic properties which provided the support for these particles as validated models of PM2.5.To further evaluate these model particle,we next evaluated cellular effects of all 63 FUPs including seven blank FUPs and FUPs that adsorb one,two or four pollutants(As(?),Pb2+,Cr(VI)and BaP).Cell viability test demonstrated that it is the adsorbed pollutants that produced the most cytotoxicity.To find out how PM2.5 and FUPs particles caused cell death,we first investigated whether they induced cellular oxidative stress.We found that ROS increased with the payloads of pollutants and ROS induction was both cell-,organ-and pollutant-dependent.As(?)and Cr(?)induced serious damage in lung cells.However,kinedy cells are more sensitivity to Pb2+.Additionally,analysis of results also indicated that cellular effects from multiple pollutants were combinations of additive or synergistic effects.We next examined cell apoptosis induction by PM2.5 and model FUP particles.Similar results were found in apoptosis.Finally,our findings indicate that 1)only certain pollutants in the payloads of PM2.5 are responsible for causing cellular oxidative stress,cell apoptosis,and cytotoxicity while the particle carriers are much less toxic;2)pollutant-induced cellular oxidative stress and oxidative stress-triggered apoptosis are identified as one of the dominant mechanisms for PM2.5-induced cytotoxicity;3)each specific toxic component on PM2.5(such as As,Pb,Cr or BaP)mainly affects its specific target organ(s)and,adding together,these pollutants may cause synergistic or just additive effects.Our findings demonstrate that reductionism concept and model PM2.5 particle library approach are very effective in our endeavor to search for a better understanding of PM2.5-induced health effects. |
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