Development of a fully bio-based pH-responsive nanocomposite for targeted 5-fluorouracil delivery: synthesis, characterization, and cytotoxicity study.

This study reports the design, synthesis, and evaluation of a pH-responsive nanocarrier system for the controlled delivery of 5-fluorouracil (5-FU), a widely used chemotherapeutic agent. A fully bio-based metal-organic framework (Bio-MOF) was synthesized and subsequently loaded with 5-FU (5-FU@Bio-MOF). To enhance control over drug release, the 5-FU@Bio-MOF was further coated with a biopolymer composed of chitosan (CH) and sodium alginate (SA). Comprehensive physicochemical characterization, including Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and Powder X-ray diffraction (PXRD), confirmed the successful synthesis of the Bio-MOF and effective encapsulation of 5-FU. Swelling and biodegradation behaviors were evaluated under physiological (pH 7.4) and acidic (pH 5.5) conditions to simulate normal and tumor microenvironments, respectively. Both systems exhibited pH-responsive swelling, with the CH/SA-coated 5-FU@Bio-MOF demonstrating enhanced swelling capacity and more controlled degradation. In vitro drug release studies revealed sustained, pH-dependent 5-FU release, with significantly higher release under acidic conditions, indicating the potential for tumor-targeted delivery. Cytotoxicity assays performed on 3 T3 fibroblasts and SH-SY5Y neuroblastoma cells demonstrated high biocompatibility toward normal cells and pronounced cytotoxicity against cancer cells. Notably, the CH/SA-coated 5-FU@Bio-MOF exhibited superior control over drug release and biocompatibility, whereas the uncoated 5-FU@Bio-MOF showed greater anticancer efficacy. These results underscore the potential of bio-based MOF systems-particularly those functionalized with biopolymer coatings-as effective and sustainable nanocarriers for targeted cancer therapy.