Fabrication of protein–inorganic biohybrid as an imageable drug delivery system comprising transferrin, green fluorescent protein, and copper phosphate

Organic–inorganic biohybrids have recently garnered attention for biomedical applications owing to their outstanding catalytic activity and biocompatibility. However, their efficacy in enhancing specificity toward drug targets remains limited. Here, we developed a transferrin–doxorubicin (TRF–DOX) complex and green fluorescence protein (GFP)-conjugated copper (Cu) phosphate (TRF–DOX@GFP@Cu biohybrid) for use as an imageable drug delivery system (DDS). TRF was utilized to increase the affinity of drug carriers for TRF receptors on cancer cells, and DOX was selected as a model drug. Additionally, GFP provides fluorescence properties for bioimaging and Cu ions serve as the skeleton for forming the flower-shaped inorganic material. By adjusting the concentrations of TRF–DOX and GFP with 25 mg mL⁻¹ of Cu precursors, six flower-shaped TRF–DOX@GFP@Cu biohybrids were fabricated. Among these, biohybrid-5 (prepared using 0.05 mg mL⁻¹ TRF–DOX and 0.10 mg mL⁻¹ of GFP with 25 mg mL⁻¹ of Cu ions) exhibited the strongest fluorescence. We characterized the morphology, composition, functional groups, and specific surface area of the TRF–DOX@GFP@Cu biohybrid. Biohybrid-5 had a specific surface area of 37.508 m² g⁻¹ and could effectively bind to A549 lung cancer cells as shown by fluorescence imaging. The novel TRF–DOX@GFP@Cu biohybrid fabricated in this study has potential as a DDS in the treatment of lung cancer.