Multi-stimuli responsive carrier systems, specifically targeting tumor cells are of high significance to improve the efficacy of cancer chemotherapy. In the present study, we have developed, characterized, and biologically evaluated magnetic casein-calcium ferrite hybrid biopolymeric carrier conjugated with biotin for targeted delivery of cinnamaldehyde to lung carcinoma. The dual stimuli-responsive carrier was successfully synthesized with small size, good stability, and high drug encapsulation efficiency. Natural drug cinnamaldehyde was encapsulated in the hybrid carrier, on which biotin was conjugated to facilitate selective cellular uptake. The prepared drug-carrier system exhibited pH-responsive drug release behavior with a higher release rate under acidic conditions, which can be effectively applied in targeted cancer chemotherapy. The superparamagnetic nature of calcium ferrite enabled magnetically-modulated drug delivery with faster drug release, reaching 85.5% within 4 h, in response to magnetic field stimulus. Kinetic modeling of drug release projected the diffusion-controlled release mechanism. Cell viability assay performed on L929 fibroblast and A549 lung cancer cells verified the biocompatibility and cytotoxicity of the developed formulation, respectively. The nanohybrid carrier significantly increased the anticancer potential of cinnamaldehyde with an 18-fold reduction in the IC 50 value, signifying the biotinfunctionalized protein-inorganic nanohybrid as an efficient multifunctional platform for targeted drug delivery.
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