To prepare a targeted delivery system of quercetin metal complex loaded with doxorubicin and to investigate its pharmaceutical properties and anti-tumor capability.

With quercetin as the ligand, the optimal bimetallic complex carrier was prepared and screened by adjusting the molar ratios of manganese to copper, and the drug-loaded nanoparticles with the best encapsulation efficiency and drug loading were screened by further adjusting the dosage of doxorubicin. Finally, the targeted drug delivery system was prepared by chondroitin sulfate modification. The physicochemical properties of the nanoparticles such as particle size, Zeta potential, infrared spectrum and ultraviolet spectrum, were characterized. Then, the in vitro drug release behavior, glutathione (GSH) degradation capability, reactive oxygen species (ROS) production capability and blood compatibility were investigated. Finally, the safety and anti-tumor activity were investigated using 3T3 and B16F10 cell lines.

The blank carrier synthesized at the optimal manganese-copper ratio of 2∶1 exhibited the best anti-tumor activity. When the dosage of doxorubicin was 0.05 mmol·L^-1, the prepared nano-delivery system had the best drug loading and encapsulation efficiency, which were (15.89±0.34)% and (90.21±0.45)%, respectively. A targeted drug delivery system was then prepared after modification with 30% chondroitin sulfate. Various characterizations confirmed the successful preparation of the bimetallic complex targeted drug delivery system, with suitable particle size and high encapsulation efficiency and drug loading. The delivery system showed good drug release under pH 5.0 condition containing 10 mmol·L^-1 GSH, and exhibited favorable GSH degradation capability, ROS production capability, blood compatibility, cytocompatibility, and tumor cytotoxicity.

In this study, a targeted drug delivery system loaded with doxorubicin metal complexes was successfully prepared by screening the metal ratio and doxorubicin dosage, followed by chondroitin sulfate modification. The system achieved high drug loading and favorable drug release behavior. This therapeutic strategy using quercetin metal complexes and doxorubicin exerts synergistic anti-tumor effects through combined chemotherapy and chemodynamic therapy, which may provide new ideas for enhancing synergistic anti-tumor efficacy.