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

Abstract A successful investigation was conducted on the in situ modification of MIL‐101(Fe)‐NH 2 with quercetin and its controlled release under various pH conditions. MIL‐101(Fe)‐NH 2 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)‐NH 2 exhibited a smaller surface area compared to MIL‐101(Fe)‐NH 2 , 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)‐NH 2 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)‐NH 2 followed the Ritger‐Peppas kinetic model, suggesting non‐Fickian diffusion. The MIL‐101(Fe)‐NH 2 nanocarriers, with in situ ‐loaded quercetin, demonstrated promising potential for pH‐triggered drug release. Additionally, the safety of MIL‐101(Fe)‐NH 2 in biological models and the anticancer efficacy of quercetin were evaluated in vitro using two liver cancer cell lines.