## 4 Conclusions  
In summary, potential therapeutic applications of Zr-MOFs were investigated by loading Mitoxantrone in UiO-66 and UiO-66-NH\({}_{2}\), followed by in vitro release studies in water and PBS. The results underscore the significance of optimizing the size of these MOFs and the loading capacity with a focus on enhancing cytotoxicity towards neoplastic cells. Both UiO-66 and UiO-66-NH\({}_{2}\) exhibited high drug loading capacities of 40 wt% and 21 wt%, respectively, positioning them as promising candidates for drug delivery systems in neoplastic cell lines. The observed negative impact on cell viability across various cell lines, coupled with the slow-release characteristics of MOFs, emphasises their controlled and gradual drug release over an extended period. Computational studies provided additional insights for the interaction between the drug molecules and the MOFs, predicting a clogging of the tetrahedral pores for UiO-66-NH\({}_{2}\) results into a lower loading capacity at a higher concentration, which was in agreement with the experimental findings. The sustained and controlled release profile of UiO-66-NH\({}_{2}\)-MTX holds potential for mitigating side effects and improving cancer treatment efficacy. However, the non-selective impact observed on 'normal' MCF10A breast cells poses a challenge to the desired reduction in side effects. Thus, further exploration is warranted to refine MOFs for enhanced selectivity and minimal adverse effects. Subsequent studies should delve into the underlying mechanisms influencing the differential responsiveness of cell lines to these compounds. The tunable nature of MOFs provides a diverse range of possible biodegradation kinetics. However, the actual durability of MOFs in bodily fluids and the impact of protein corona formation on modifying release profiles necessitate a thorough validation in future studies. This study sets the stage for continued exploration and refinement of MOFs, paving the way for their potential in innovative drug delivery systems with enhanced therapeutic efficacy and reduced side effects. The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/app14051902/s1](https://www.mdpi.com/article/10.3390/app14051902/s1)]([https://www.mdpi.com/article/10.3390/app14051902/s1](https://www.mdpi.com/article/10.3390/app14051902/s1)), Figure S1: Schematic presentation for synthesis of MOFs; Figure S2: MTX loading and optimisation experiments; Figure S3: Images of filtrate obtained after washing the MTX loaded MOFs; Figure S4: Calibration curve of MTX; Figure S5: Schematic presentation for in vitro release; Figure S6: Images of neoplastic and normal cell line; Figure S7: DLS for the particle size distribution of (A) UiO-66, (B) UiO-66-MTX, (C) UiO-66-NH2, and (D) UiO-66-NH2-MTX. Each peak in the diagram represents an average of 12 measurements for 3 peaks (in different colours) per diagram. Table S1: Optimization of MTX concentration loaded on UiO-66; Table S2: Optimization of MTX concentration loaded on UiO-66 (Set-2); Table S3: Optimization of MTX concentration loaded on UiO-66-NH\({}_{2}\); Table S4: Repeats of MTX concentration (1:1) loaded on UiO-66; Table S5: Repeats of MTX concentration (1:0.25) loaded on UiO-66-NH\({}_{2}\). M.S. : Execution of concept, practical experiments, characterisation of materials, data collection, data analysis, writing, and manuscript preparation. K.R.-S.; Supervision and review and editing of manuscript. K.P. ; Supervision, conceptualisation, and review and editing of manuscript. M.A.A. ; Experiment and review and editing of manuscript. A.R. ; Supervision, conceptualisation, and review and editing of manuscript. S.N. ; Supervision, conceptualisation, and review and editing of manuscript. J.E. ; Supervision, conceptualisation, and review and editing of manuscript. All authors have read and agreed to the published version of the manuscript. A.R.