School of Life Sciences, Jilin University, Changchun 130012, China.
Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Molecules. 2019 Sep 30;24(19):3540. doi: 10.3390/molecules24193540.
Glioma is one of the most aggressive and common malignant brain tumors. Due to the presence of the blood-brain barrier (BBB), the effectiveness of therapeutics is greatly affected. In this work, to develop an efficient anti-glioma drug with targeting and which was able to cross the BBB, cell-penetrating peptides (R8) and transferrin co-modified doxorubicin (DOX)-loaded liposomes (Tf-LPs) were prepared. Tf-LPs possessed a spherical shape and uniform size with 128.64 nm and their ξ-potential was 6.81 mV. Tf-LPs were found to be stable in serum within 48 h. Uptake of Tf-LPs in both U87 and GL261 cells was analyzed by confocal laser scanning microscopy and by flow cytometry. Tf-LPs were efficiently taken up by both U87 and GL261 cells. Moreover, Tf-LPs exhibited sustained-release. The cumulative release of DOX from Tf-LPs reached ~50.0% and showed excellent anti-glioma efficacy. Histology of major organs, including brain, heart, liver, spleen, lungs and kidney, and the bodyweight of mice, all indicated low toxicity of Tf-LPs. In conclusion, Tf-LPs showed great promise as an anti-glioma therapeutic agent.
神经胶质瘤是最具侵袭性和常见的恶性脑肿瘤之一。由于血脑屏障（BBB）的存在，治疗效果受到很大影响。在这项工作中，为了开发一种具有靶向性且能够穿透血脑屏障的高效抗神经胶质瘤药物，我们制备了细胞穿透肽（R8）和转铁蛋白共修饰的阿霉素（DOX）载脂蛋白（Tf-LPs）。Tf-LPs 呈球形且粒径均匀，粒径为 128.64nm，ξ-电位为 6.81mV。Tf-LPs 在血清中 48 小时内稳定。通过共聚焦激光扫描显微镜和流式细胞术分析了 Tf-LPs 在 U87 和 GL261 细胞中的摄取情况。Tf-LPs 能够被 U87 和 GL261 细胞有效摄取。此外，Tf-LPs 表现出持续释放。Tf-LPs 中 DOX 的累积释放量达到约 50.0%，显示出优异的抗神经胶质瘤疗效。包括脑、心、肝、脾、肺和肾在内的主要器官的组织学以及小鼠的体重均表明 Tf-LPs 的毒性较低。总之，Tf-LPs 作为一种抗神经胶质瘤治疗剂具有很大的应用前景。
