Dynamic pH‐Responsive Release and Biological Impact of In Situ Quercetin‐Modified MIL‐101(Fe)‐NH₂

Abstract A successful investigation was conducted on the in situ modification of MIL‐101(Fe)‐NH₂ with quercetin and its controlled release under various pH conditions. MIL‐101(Fe)‐NH₂ was synthesized using an electrochemical method at room temperature (15 volts, 30 min). The formation of the material was confirmed through comprehensive analyses, including PXRD, FTIR, and TGA. Nitrogen sorption isotherm measurements revealed that Qu@MIL‐101(Fe)‐NH₂ exhibited a smaller surface area compared to MIL‐101(Fe)‐NH₂, with both materials classified as mesoporous. Transmission electron microscopy (TEM) clearly depicted the materials’ octahedral microspindle morphology. The cumulative percent release (CPR) of quercetin from Qu@MIL‐101(Fe)‐NH₂ over 72 h was determined to be 53.45 % at pH 1.2, 19.48 % at pH 4.8, and 5.87 % at pH 7.4. Notably, quercetin release in the acidic microenvironment representative of cancer cells (pH 4.8) was nearly four times higher than under physiological conditions (pH 7.4). Kinetic release studies indicated that quercetin release from Qu@MIL‐101(Fe)‐NH₂ followed the Ritger‐Peppas kinetic model, suggesting non‐Fickian diffusion. The MIL‐101(Fe)‐NH₂ nanocarriers, with in situ‐loaded quercetin, demonstrated promising potential for pH‐triggered drug release. Additionally, the safety of MIL‐101(Fe)‐NH₂ in biological models and the anticancer efficacy of quercetin were evaluated in vitro using two liver cancer cell lines.