Folate-Modified Smart Responsive Nanosystems for Enhancing Anti-Tumor Therapy Through Calcium Overload and Chemotherapy.

Objective: The combination of DOX and 5-Fu is an important chemotherapeutic regimen but lacks targeting to solid tumor sites. Precise drug delivery via folate-modified nanomaterials is an important measure to improve efficacy and reduce toxicity.

Methods: CaCO₃ nanoparticles served as the carrier for loading DOX and 5-Fu, followed by encapsulation with folic acid-modified polydopamine (PDA) to form a smart dual drug-carrying nanosystem called FA-DCFP. The nanoparticles (NPs) were characterized and the release kinetics and anti-tumor effectiveness of FA-DCFP were studied in vitro and in vivo.

Results: The prepared nanoparticles had an average particle size of 188.79±0.93nm and exhibited pH-sensitive drug release. Cellular experiments demonstrated that the synergistic effect of tumor cell calcium overload and chemotherapy resulted in tumor cell death. Small animal in vivo imaging showed that FA-DCFP was well enriched in the tumour region. In vivo experiments demonstrated that FA-DCFP exhibited significant inhibition of tumour growth, attenuation of toxic side effects, and good biosafety compared to other groups.

Conclusion: An intelligent-responsive nano-dual drug delivery system was developed to enhance the therapeutic effectiveness of tumors through calcium overload synergistic chemotherapy, offering a novel approach to tumor treatment.