The drug loading capacity prediction and cytotoxicity analysis of metal–organic frameworks using stacking algorithms of machine learning

Metal–organic frameworks (MOFs) have shown excellent performance in the field of drug delivery. Despite the synthesis of a vast array of MOFs exceeding 100,000 varieties, certain formulations have exhibited suboptimal performance characteristics. Therefore, there is a pressing need to enhance their efficacy by identifying MOFs with superior drug loading capacities and minimal cytotoxicity, which can be achieved through machine learning (ML). In this study, a stacking regression model was developed to predict drug loading capacity and cytotoxicity of MOFs using datasets compiled from various literature sources. The model exhibited exceptional predictive capabilities, achieving R2 values of 0.907 for drug loading capacity and 0.856 for cytotoxicity. Furthermore, various model interpretation methods including partial dependence plots, individual conditional expectation, Shapley additive explanation, decision tree, random forest, CatBoost Regressor, and light gradient-boosting machine were employed for feature importance analysis. The results revealed that specific metal atoms such as Zn, Cr, Fe, Zr, and Cu significantly influenced the drug loading capacity and cytotoxicity of MOFs. Through model validation encompassing experimental validation and computational verification, the reliability of the model was thoroughly established. In general, it is a good practice to use ML methods for predicting drug loading capacity and cytotoxicity analysis of MOFs, guiding the development of future property prediction methods for MOFs.