Wang Qi, Wei Na, Liu Xiaofeng, Chang Alex, Luo Kathy Qian
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Department of Oncology, Johns Hopkins Singapore, Singapore.
Oncotarget. 2017 Feb 14;8(7):12013-12030. doi: 10.18632/oncotarget.14481.
The Poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (mPEG-PLGA) nanoparticles carrying acetyltanshinone IIA (ATA), a novel anti-breast cancer agent, were prepared by ultrasonic emulsion method to enhance the bioavailability and reduce the toxicity. Systematic optimization of encapsulation process was achieved using an orthogonal design. Drug efficacy analysis showed that ATA nanoparticles were as effective as free ATA against estrogen receptor positive breast cancer cells, but much less toxic towards human endothelial cells. Furthermore, in zebrafish, ATA nanoparticles displayed much lower toxicity than free ATA. More importantly, the blood concentration of ATA nanoparticles indicated by 24 hour-area under the curve (AUC0-24h) was 10 times higher than free ATA. These results indicated the potential of ATA-loaded mPEG-PLGA nanoparticles for the delivery of ATA in a clinical formulation, and their potential for use in tumor therapy in the future.
采用超声乳化法制备了负载新型抗乳腺癌药物乙酰丹参酮IIA（ATA）的聚（乙二醇）甲醚-嵌段-聚（丙交酯-乙交酯）（mPEG-PLGA）纳米粒，以提高其生物利用度并降低毒性。通过正交设计实现了包封工艺的系统优化。药效分析表明，ATA纳米粒对雌激素受体阳性乳腺癌细胞的疗效与游离ATA相当，但对人内皮细胞的毒性要小得多。此外，在斑马鱼中，ATA纳米粒的毒性比游离ATA低得多。更重要的是，24小时曲线下面积（AUC0-24h）表明，ATA纳米粒的血药浓度比游离ATA高10倍。这些结果表明，负载ATA的mPEG-PLGA纳米粒在临床制剂中递送ATA具有潜力，且未来在肿瘤治疗中具有应用潜力。
