Dermatan sulfate-recognized UiO-66 metal-organic frameworks: An active and passive targeting nanomedicine for methotrexate delivery.

This study introduces a novel drug delivery system (DDS) by integrating zirconium-based metal-organic frameworks (UiO-66) with glycosaminoglycans, specifically dermatan sulfate (DS), to achieve an active and passive targeting nanomedicine. The synthesized UiO-66/DS nanocomposite demonstrated successful structural validation and exhibited a pH-dependent release profile for methotrexate (MTX), with 75 % release at acidic pH 4.5 (simulating acidic environment of intracellular compartments) versus <30 % at physiological pH 7.4 over 96 h. Cytotoxicity assays revealed enhanced cancer cell apoptosis in MCF-7 cell line via CD44 receptor-mediated uptake, coupled with minimal hemolytic activity (<4 %), underscoring the system's therapeutic safety. These findings highlight the potential of UiO-66/DS nanocomposite as a dual-targeted platform for anticancer therapies, taking advantage of its pH-responsive behavior in acidic tumor microenvironments and its enhanced cellular interactions mediated by conjugating sulfated polysaccharide.