【摘要】 目的:制备载阿霉素的槲皮素金属配合物靶向递送系统，并考察其制剂学性质与抗肿瘤能力。方法:以槲皮素为配体，通过调节锰铜摩尔比制备并筛选出最优双金属配合物载体，进一步调节阿霉素的投药量，筛选出最佳包封率和载药量的载药纳米粒，通过硫酸软骨素修饰制备靶向药物递送系统。对纳米粒进行颗粒粒径、Zeta电位、红外光谱、紫外光谱等理化性质表征；考察其体外释药行为、还原型谷胱甘肽（glutathione, GSH）分解能力、活性氧（reactive oxygen species, ROS）产生能力、血液相容性等；通过3T3和B16F10细胞系考察其安全性与抗肿瘤活性。结果:本研究筛选出锰铜比为2∶1时合成的空白载体具有最佳抗肿瘤活性；当阿霉素投药量为0.05 mmol·L^-1时制备的纳米递送系统具有最佳载药量和包封率，靶向药物递送系统分别为（15.89±0.34）%和（90.21±0.45）%;最终经30%的硫酸软骨素修饰后制备靶向药物递送系统。各种表征表明本研究成功制备了双金属配合物靶向药物递送系统，粒径适宜且具有较高包封率和载药量。该递送系统在含GSH(10 mmol·L^-1)的pH 5.0条件下表现出较好的释药情况，具有良好的GSH分解能力、ROS产生能力、血液相容性、细胞相容性和肿瘤细胞毒性。结论:本研究通过筛选金属比例、筛选投药量和修饰硫酸软骨素制备得到载阿霉素金属配合物的靶向药物递送系统，载药量高，具有良好的释药行为，这种使用槲皮素金属配合物与阿霉素的治疗策略通过化疗和化学动力学疗法协同抗肿瘤，可为协同促进抗肿瘤疗效提供新思路。更多还原

【Abstract】 Objective: To prepare a targeted delivery system of quercetin metal complex loaded with doxorubicin and to investigate its pharmaceutical properties and anti-tumor capability. Methods: 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. Results: 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. Conclusion: 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.更多还原