Biodegradable organosilica-shelled Zn-MOF nanocarriers for selective cancer theranostics: Dual-domain rosmarinic acid loading, pH-responsive release and fluorescence imaging

A biodegradable theranostic nanoplatform was engineered by integrating a zinc-based metal–organic framework (Zn-MOF) core with a periodic mesoporous organosilica (E4S) shell to address the limited stability and biocompatibility of conventional MOF drug carriers. The organosilica shell not only enhanced the structural integrity and hydrophilicity of the Zn-MOF but also introduced a biodegradable interface suitable for biomedical applications. Fluorescein isothiocyanate (FITC) was further conjugated onto the shell to provide fluorescence imaging capability. Rosmarinic acid (RA), a poorly water-soluble natural anticancer compound, was employed as a model therapeutic cargo. Systematic adsorption studies revealed a dual-domain loading mechanism involving both the porous Zn-MOF framework and the mesostructured organosilica shell, resulting in high loading capacity and favorable adsorption kinetics. The resulting RA@Zn-MOF@E4S nanocarrier exhibited sustained and pH-responsive release behavior, with significantly accelerated drug release under mildly acidic conditions relevant to tumor-associated and intracellular environments. Cellular studies demonstrated preferential uptake of Zn-MOF@E4S by C-26 colon cancer cells compared with L929 fibroblast cells, indicating preferential internalization by cancer cells under the tested conditions. Consequently, RA@Zn-MOF@E4S displayed enhanced anticancer efficacy while maintaining relatively low cytotoxicity toward normal cells at moderate concentrations. In addition, FITC-functionalized nanoparticles enabled effective fluorescence-based cellular imaging, providing simultaneous therapeutic and diagnostic functionality. These findings demonstrate that biodegradable organosilica-shelled Zn-MOF nanostructures represent a promising theranostic platform for the delivery of poorly soluble anticancer agents, combining high loading capacity, pH-responsive release, preferential cancer-selective cellular uptake, and fluorescence imaging capability within a single hybrid nanocarrier system.