beta-Cyclodextrin-functionalized Zr-sulfonamide MOF novel pH-responsive nano platform for breast and lung cancer

Alavinia, Sedigheh;  Ghorbani-Vaghei, Ramin;  Derakhshandeh, Katayoun;  Emami, Nafiseh: Uroomiye, Seyed Sepehr:Babaei, Milad 

Despite significant advancements in cancer therapies, lung and breast cancers continue to pose serious challenges, remaining among the most prevalent and lethal forms of the disease. This study investigates an innovative approach to enhance drug delivery and treatment efficacy through the synthesis of sulfonamide UiO-MOF (Metal-Organic Framework) and its derivative, Sul-UiO-MOF-ABA-(3-cyclodextrin, specifically designed for the loading of paclitaxel (PTX). The unique synergy of (3-cyclodextrin and a sulfonamide MOF significantly improves PTX loading and enhances therapeutic effectiveness, demonstrating considerable potential for cancer treatment. Our findings indicate that the PTX@3 T formulation exhibits a remarkable pH-responsive release profile, with 84.16% of the drug released at a reduced pH of 5.3, conforming to first-order kinetic models. The entrapment efficiencies for PTX@2 T and PTX@3 T were notable at 70.3% and 90.25%, respectively. Inefficacy tests on the MCF-7 breast cancer cell line, the IC50 values for PTX, PTX@2 T, and PTX@3 T were 24.91, 9.87, and 10.00 mu g/mL, respectively, correlating with apoptosis rates of 31.14%, 70.68%, and 96.56%. Similarly, for the A-549 lung cancer cell line, the IC50 values were 9.75, 1.82, and 5.86 mu g/ml, with apoptosis rates of 38.25%, 10.55%, and 11.50%, respectively.Importantly, Sul-UiO-MOF and Sul-UiO-MOF-ABA-(3CD demonstrated excellent biocompatibility, maintaining approximately 100% cell viability in HEK293 cells after 48 h, indicating a favorable safety profile for therapeutic use. Thus, PTX@3 T emerges as a compelling "smart" drug delivery system, offering a promising avenue for improved cancer therapy that warrants further investigation