Zhang Yuebin, Yu Jia, Zhang Lifeng, Cai Jiabin, Cai Doute, Lv Chengjie
Department of General Surgery, Children's Hospital Zhejiang University School of Medicine, No. 57 Zhugan Lane, Hangzhou, Zhejiang, 310003, China.
Department of ICU, Children's Hospital Zhejiang University School of Medicine, Hangzhou, 310003, China.
Tumour Biol. 2016 Feb;37(2):2703-8. doi: 10.1007/s13277-015-4106-7. Epub 2015 Sep 24.
For effective therapy for glioma, it is essential for chemotherapeutics to pass the blood-brain barrier to target glioma cells with little side effects to surrounding normal cells. In this study, we prepared doxorubicin-polybutylcyanoacrylate nanoparticles (Dox-PBCA-NP) and assessed its inhibition effects on glioma both in vitro and in vivo. Dox-PBCA-NP was prepared using the emulsion polymerization method. The size and size distribution of nanoparticles were measured by Malven laser mastersizer and the morphology was observed under transmission electron microscope. Drug loading (DL) and entrapment efficiency (EE) of doxorubicin in the nanoparticles were measured by UV spectra. The proliferation of C6 glioma cells was detected by MTT assay, and cell cycle was analyzed by flow cytometry. The expression of telomerase was detected by immunocytochemical analysis. The anti-tumor efficiency of Dox-PBCA-NP was assessed in C6 glioma intracranial implant rat model. The average diameter of NP-Dox was 120 nm, DL was 10.58 %, and EE was 87.43 %. We found that the cytotoxicity of Dox-PBCA-NP was lower than Dox in vitro. In vivo, Dox-PBCA-NP could transport more Dox into tumors compared to contralateral control, and the life span was longer than Dox. Moreover, Dox-PBCA-NP had less cardiotoxicity than Dox. Taken together, our results suggest that Dox-PBCA-NP exhibits better therapeutic effects against glioma and fewer side effects and is a potential nano-scale drug delivery system for glioma chemotherapy.
为了实现对胶质瘤的有效治疗，化疗药物必须穿过血脑屏障，靶向胶质瘤细胞，同时对周围正常细胞产生极小的副作用。在本研究中，我们制备了阿霉素-聚氰基丙烯酸正丁酯纳米粒（Dox-PBCA-NP），并评估了其在体外和体内对胶质瘤的抑制作用。采用乳液聚合法制备Dox-PBCA-NP。通过马尔文激光粒度分析仪测量纳米粒的尺寸和尺寸分布，并在透射电子显微镜下观察其形态。通过紫外光谱法测定纳米粒中阿霉素的载药量（DL）和包封率（EE）。采用MTT法检测C6胶质瘤细胞的增殖情况，并通过流式细胞术分析细胞周期。通过免疫细胞化学分析检测端粒酶的表达。在C6胶质瘤颅内植入大鼠模型中评估Dox-PBCA-NP的抗肿瘤效果。NP-Dox的平均直径为120nm，DL为10.58%，EE为87.43%。我们发现，Dox-PBCA-NP在体外的细胞毒性低于阿霉素。在体内，与对侧对照组相比，Dox-PBCA-NP能将更多的阿霉素转运到肿瘤中，且生存期比阿霉素更长。此外，Dox-PBCA-NP的心脏毒性比阿霉素更小。综上所述，我们的结果表明，Dox-PBCA-NP对胶质瘤具有更好的治疗效果且副作用更少，是一种潜在的用于胶质瘤化疗的纳米级药物递送系统。
