Cytotoxicity And Inflammatory Responses Of Several Kinds Of Colloidal Particles And Their Inhibitory Methods

Recently,due to their unique physical and chemical properties,colloidal particles have attracted much attention in many fields including biomedical materials.However,the potential detriment of colloidal particles on organisms during their applications is a big concern.Therefore,a comprehensive toxicity evaluation of colloidal particles is of great significance.At the same time,elimination or suppression of the toxicity and inflammatory responses caused by colloidal particles is becoming an indispensable issue which should be put on the agenda.In this paper,the cytotoxicity,genotoxicity and impact on the differentiation potential of mesenchymal stem cells(MSCs)by three kinds of nanodiamonds(NDs)with different surface chemistry is investigated.Attention is paid to the inflammatory activation of four kinds of albumin-modified chitosan particles to macrophages and their immune response in human whole blood.Finally,toxicity inhibition and elimination of CuO nanoparticles and haze PM2.5 suspension by particles with the ability to chelate metal ions or scavenge reactive oxygen species(ROS)are studied.The surface properties of particles are important factors affecting their interaction with cells.The biological effects of NDs with different surface chemistry(carboxyl group(ND-COOH),amino group(ND-NH3+)and poly(ethylene glycol)(PEG)(ND-PEG))on MSCs was assessed in vitro.All three kinds of NDs showed similar aggregation size(-100 nm)and surface zeta potential(～-10mV)in cell culture medium.The cytotoxicity of NDs was concentration-dependent and their surface chemistry had an impact on their toxicity intensively.The ROS level and genotoxicity of NDs were evaluated.The toxicity of ND-NH3+ was higher than ND-COOH and ND-PEG.In addition,the effects of three kinds of NDs on the potential differentiation of MSCs were studied.All the NDs did not show significant impact on the osteogenic differentiation of MSCs,whereas the ND-COOH and ND-PEG slightly impaired the adipogenic differentiation.After the colloidal particles intrude into huaman body,the immune response may be activated,after which the particles trigger some inflammatory responses and will be cleared away eventually.Four kinds of chitosan(CS)particles modified with different kinds and quantity of human serum albumin(HSA)and ovalbumin(OVA),i.e.CS@HSA-10,CS@HSA-57,CS@OVA-13 and CS@OVA-65 were prepared by an emulsion crosslinking method.After co-incubation with macrophages,the secretion of inflammatory cytokines induced by CS@HSA was higher than CS@HSA when the surface proteins were modified at the same level.After they were involved in human whole blood,the phagocytosis by granulocytes and monocytes,inflammatory factors secretion in the plasma,and platelet activation were all higher for CS@OVA than CS@HSA particles.OVA modification may enhance the inflammatory response of CS particles to macrophages,as well as the immune response in human whole blood,while the HSA modification can attenuate these effects.Based on the toxic mechanism of metal oxide particles which is always associated with the release of metal ions after their uptake,three kinds of chitosan nanoparticles(CS NPs)modified with different types of amino acids,i.e.lysine-modified(Ly-CS)and glutamic acid-modified(Glu-CS),and sodium borohydride reduction(R-CS)were prepared to investigate their ability of suppressing the cytotoxicity induced by CuO NPs.The chelating efficiency of the CS NPs followed the order Ly-CS>Glu-CS>R-CS.The CS NPs showed minimal or no toxicity to three different cell lines(HepG2,A549,and RAW264.7 cells)at 100μg/mL with similar cell internalization and exocytosis processes.All three CS NPs,especially Ly-CS and Glu-CS NPs,efficiently suppressed the cytotoxicity induced by CuO NPs,and reduced the intracellular ROS level.Among the three kinds of CS-NPs,the Ly-CS NPs most efficiently reduced the intracellular ROS level induced by CuO NPs,probably due to the chelation of released Cu2+ ions,resulting in the suppression of cytotoxic effects.Stimuli-responsive materials can realize the controlled release of the loaded cargos on demond in response to the external or internal stimulus.It is known that the cytotoxicity of nanoparticles is always accompanied by an increase of intracellular ROS level.ROS-responsive poly-(1,4-phenyleneacetonedimethylene thioketal)(PPADT)particles with and without’ loading of immunosuppressant tacrolimus(FK506)(PPADT@FK506)were prepared to study their suppression effect towards the cytotoxicity induced by PM2.5 suspension collected from three different regions.The Nile red(NR)could be effectively released from the NR-loaded particles(PPADT@NR)when being co-incubated with PM2.5 in A549 and RAW264.7 cells,suggesting the ROS responsiveness of PPADT particles.After the co-incubation of A549 and RAW264.7 cells with PPADT particles and PM2.5 suspension,the cytotoxicity induced by PM2.5 suspensions could almost be completely eliminated and the intracellular ROS could be efficiently consumed.Besides,the inflammatory factors secreted by RAW264.7 cells were also decreased after the addition of PPADT@FK506 particles,indicating the ability of PPADT@FK506 in reducing the inflammatory responses caused by PM2.5 suspension.The results of animal experiments also show that the drug-loaded particles can effectively inhibit the in vivo toxicity and inflammation induced by PM2.5.