Key Laboratory of Synthetic and Natural Functional Molecular Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710069, P. R. China.
Nanoscale. 2015 Jul 7;7(25):11155-62. doi: 10.1039/c5nr01382h.
Dextran-coated superparamagnetic iron oxide nanoparticles (DSPIONs) have gained considerable interest, because of their biocompatibility and biosafety in clinics. Doxorubicin (Dox), a widely used chemotherapeutic drug, always has limited applications in clinical therapy due to its serious side effects of dose-limiting irreversible cardiotoxicity and myelo suppression. Herein, DSPIONs were synthesized and developed as magnetic carriers for doxorubicin. The Dox-DSPION conjugates were evaluated in the in vitro test of Dox release, which showed pH-dependence with the highest release percentage of 50.3% at pH 5.0 and the lowest release percentage of 11.8% in a physiological environment. The cytotoxicity of DSPIONs and Dox-DSPIONs evaluated by the MTT assay indicated that DSPIONs had no cytotoxicity and the conjugates had significantly reduced the toxicity (IC50 = 1.36 μg mL(-1)) compared to free Dox (IC50 = 0.533 μg mL(-1)). Furthermore, confocal microscopic data of cell uptake suggest that less cytotoxicity of Dox-DSPIONs may be attributed to the cellular internalization of the conjugates and sustainable release of Dox from the formulation in the cytoplasm. More importantly, the results from the rabbit VX2 liver tumor model test under an external magnetic field showed that the conjugates had approximately twice the anti-tumor activity and two and a half times the animal survival rate, respectively, compared to free Dox. Collectively, our data have demonstrated that Dox-DSPIONs have less toxicity with better antitumor effectiveness in in vitro and in vivo applications, suggesting that the conjugates have potential to be developed into chemo-therapeutic formulations.
葡聚糖包覆的超顺磁性氧化铁纳米粒子（DSPIONs）由于其在临床中的生物相容性和生物安全性而受到广泛关注。阿霉素（Dox）是一种广泛使用的化疗药物，由于其剂量限制的不可逆心脏毒性和骨髓抑制等严重副作用，其临床应用一直受到限制。在此，我们合成并开发了 DSPIONs 作为阿霉素的磁性载体。在体外阿霉素释放试验中对 Dox-DSPION 缀合物进行了评估，结果表明该缀合物具有 pH 依赖性，在 pH 5.0 时的释放百分比最高为 50.3%，在生理环境中的释放百分比最低为 11.8%。MTT 法评估的 DSPIONs 和 Dox-DSPIONs 的细胞毒性表明，DSPIONs 没有细胞毒性，与游离 Dox（IC50 = 0.533 μg mL(-1)）相比，缀合物的毒性显著降低（IC50 = 1.36 μg mL(-1)）。此外，细胞摄取的共焦显微镜数据表明，Dox-DSPIONs 的低细胞毒性可能归因于细胞内吞作用以及药物在细胞质中的持续释放。更重要的是，在外部磁场下的兔 VX2 肝肿瘤模型试验结果表明，与游离 Dox 相比，缀合物的抗肿瘤活性分别提高了约 2 倍，动物存活率提高了 2.5 倍。总之，我们的数据表明，Dox-DSPIONs 在体外和体内应用中具有较低的毒性和更好的抗肿瘤效果，表明该缀合物具有开发成化学治疗制剂的潜力。
