Prediction Models For Adsorption Capacity Of Metal Oxide Nanoparticles For Lipids

Pulmonary inhalation is the main route for metal oxide nanoparticles（Me ONPs）to enter the human body.The adsorption capacity of Me ONPs for lipids that are the main components of pulmonary surfactant,is an important factor affecting the biological effect of nanoparticles entering the human body through the respiratory tract.At present,studies on the adsorption capacity of Me ONPs for lipids are very limited.Due to the increasing variety of synthetic Me ONPs,it is necessary to establish a model to predict the adsorption capacity of Me ONPs for lipids.In this study,1,2-dipalmitoyl-sn-glycero-3-phosphocholine（DPPC）vesicles were used to simulate pulmonary surfactant,and Me ONPs were incubated with DPPC to determine the adsorption capacity of Me ONPs for DPPC.The adsorption capacity of Me ONPs for DPPC was quantitatively determined,and a model for predicting the adsorption capacity of Me ONPs for lipids was established.Adsorption experiments showed that there was no significant difference in the adsorption capacity of Me ONPs with different particle sizes（including anatase Ti O₂,In₂O₃,Al₂O₃,Ni O and Co₃O₄）for DPPC（P>0.05）,indicating that particle size was not the key factor affecting adsorption capacity of Me ONPs for DPPC.Compared with other Me ONPs in this study,rare earth metal oxides(Ho₂O₃,Dy₂O₃,Sm₂O₃,Pr₆O₁₁,Gd₂O₃,Nd₂O₃,Y₂O₃)have higher adsorption capacity for DPPC（>0.9 g/g）.The adsorption interactions of Me ONPs with DPPC were investigated using density functional theory calculations.The adsorption energy and adsorption distance between Me ONPs and phosphate groups were estimated in this study because the phosphate group is the primary site for phospholipid adsorption by Me ONPs.The adsorption simulation results show that the rare earth metal oxides with higher adsorption capacity for DPPC also have higher adsorption energy with phosphate groups,indicating that the phosphate groups at the head of DPPC play a key role in the adsorption.The correlation analysis between adsorption energy and d-band center of metal atom shows that the higher d-band center of metal atom makes it easier to adsorb with O atom of phosphate group.A model for predicting the adsorption capacity of Me ONPs for DPPC was established based on the adsorption energy of Me ONPs for phosphate groups.The results of model performance evaluation show that the model exhibits satisfactory goodness of fit(R²_adj=0.73,RMSE_tra=0.26)and robustness(Q²_cv=0.74),but the predictive ability of the model still needs to be improved(Q²_ext=0.59).In order to further improve the prediction performance of the model,the adsorption capacity of 25 kinds of Me ONPs for phosphate was measured instead of the calculated adsorption energy,and a model for predicting the adsorption capacity of Me ONPs for DPPC was established.The model performance evaluation results show that the prediction model exhibits satisfactory goodness of fit,robustness and predictive ability(R²_adj=0.79、RMSE_tra=0.23、Q_cv²=0.74、Q²_ext=0.86).The model also confirmed that the phosphoric groups in the head of DPPC are important adsorption sites of rare earth metal oxides for DPPC.In addition,the electronegativity of metal elements and the mass percentage of metal elements jointly affect the adsorption capacity of Me ONPs for DPPC,it is not conducive to the adsorption of Me ONPs for DPPC when the electronegativity of metal elements of Me ONPs is high（>1.22）.The prediction model established in this study provides basic data for evaluating adsorption capacity of Me ONPs inhaled into human body through lung for lipids,but also expands the understanding of the adsorption mechanism of Me ONPs for lipids.