Receptor-mediated PLGA nanoparticles for glioblastoma multiforme treatment
Receptor-mediated PLGA nanoparticles for glioblastoma multiforme treatment
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DOI：
10.1016/j.ijpharm.2018.04.062
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发表时间：
2018-07-10
影响因子：
5.8
通讯作者：
Pereira, M. C.
中科院分区：
文献类型：
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作者：
Ramalho, M. J.;Sevin, E.;Pereira, M. C.
多形性胶质母细胞瘤是最致命的脑肿瘤类型，现有的治疗方法只能将患者的生存期延长到大约一年。其一线治疗是基于与烷化剂替莫唑胺（TMZ）的化疗。与其他化疗药物一样，TMZ存在毒性大、生物利用度低等局限性。在这项工作中，提出了使用聚（乳酸-羟基乙酸）纳米粒子的TMZ的交付。开发了用转铁蛋白受体的0X 26型单克隆抗体功能化的稳定纳米颗粒，靶向胶质母细胞瘤肿瘤细胞，因为已知这些细胞过表达该受体。模拟生理条件研究了TMZ从纳米颗粒的释放曲线，并研究了靶向细胞内化。两个胶质母细胞瘤细胞系- U215和U87 -用于评估药物的体外细胞毒性，表明制备的纳米载体增强TMZ的抗癌活性。转铁蛋白受体的单克隆抗体的功能化被证明是有利的，在增强胶质母细胞瘤细胞的细胞内化。
Glioblastoma multiforme is the most lethal type of brain tumor and the established therapy only extends patients survival to approximately one year. Its first-line treatment is based on of chemotherapy with the alkylating agent temozolomide (TMZ). As many other chemotherapeutic drugs, TMZ presents several limitations as high toxicity and low bioavailability. The delivery of TMZ using poly(lactic-co-glycolic acid) nanoparticles is proposed in this work. Stable nanoparticles functionalized with a OX26 type monoclonal antibody for transferrin receptor were developed, targeting the glioblastoma tumor cells, since these cells are known for overexpressing this receptor. The release profile of TMZ from the nanoparticles was studied mimicking physiological conditions, and targeted cellular internalization was also investigated. Two glioblastoma cell lines - U215 and U87 - were used to evaluate the in vitro cytotoxicity of the drug, showing that the prepared nanocarriers enhance the anticancer activity of TMZ. The functionalization with the monoclonal antibody for transferrin receptor proved to be advantageous in enhancing the cellular internalization in glioblastoma cells.