The First Affiliated Hospital of Soochow University.
Department of Neurosurgery, The People's Hospital of Rizhao, Rizhao, China.
Anticancer Drugs. 2019 Jul;30(6):604-610. doi: 10.1097/CAD.0000000000000754.
Glioma is a primary intracranial malignant tumor with poor prognosis. In this study, we aimed to develop transferrin (Tf)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles to deliver temozolomide (TMZ) to glioma and evaluate their efficacy to kill glioma. TMZ-loaded nanoparticles were prepared by nanoprecipitation technique and targeted by Tf. Tf-PLGA-TMZ and PLGA-TMZ were characterized for average particle sizes and zeta potentials, cellular uptake and cytotoxicity as well as in-vitro drug release of these nanoparticles were evaluated in human glioma U87MG cells. In-vivo antiglioma efficacy of Tf-PLGA-TMZ was evaluated in nude mice. Polydispersity ratio increased from 0.132 to 0.150, while encapsulation efficiency decreased from 69.4 to 55.8% after Tf modification of PLGA-TMZ. High performance liquid chromatography test showed that Tf-targeted nanoparticles were better internalized into U87MG cells than nontargeted nanoparticles. Moreover, Tf-PLGA-TMZ significantly decreased the viability of U87MG cells compared with nontargeted nanoparticles (P<0.05). In addition, Tf-PLGA-TMZ significantly decreased tumor volume and improved the survival of nude mice injected with U87MG cells. Tf-modified PLGA nanoparticles could be used for effective delivery of TMZ and have promise for the treatment of glioma.
神经胶质瘤是一种预后不良的原发性颅内恶性肿瘤。本研究旨在制备转铁蛋白（Tf）修饰的聚乳酸-共-羟基乙酸（PLGA）纳米粒递送至神经胶质瘤部位并评价其杀伤神经胶质瘤的效果。采用纳米沉淀技术制备载替莫唑胺（TMZ）的纳米粒，并通过 Tf 进行靶向修饰。对 Tf-PLGA-TMZ 和 PLGA-TMZ 的平均粒径和 Zeta 电位、细胞摄取和细胞毒性进行了表征，并评价了这些纳米粒在人神经胶质瘤 U87MG 细胞中的体外药物释放情况。在裸鼠体内评价了 Tf-PLGA-TMZ 的抗神经胶质瘤效果。PLGA-TMZ 经 Tf 修饰后，多分散系数从 0.132 增加到 0.150，而包封率从 69.4%下降至 55.8%。高效液相色谱法检测结果表明，与非靶向纳米粒相比，Tf 靶向纳米粒更易被 U87MG 细胞内化。此外，与非靶向纳米粒相比，Tf-PLGA-TMZ 显著降低了 U87MG 细胞的活力（P<0.05）。另外，Tf-PLGA-TMZ 显著降低了荷瘤裸鼠的肿瘤体积，提高了其存活率。Tf 修饰的 PLGA 纳米粒可用于 TMZ 的有效递送，有望用于神经胶质瘤的治疗。
