a Department of Biochemistry , Ege University Faculty of Science , Izmir , Turkey.
Artif Cells Nanomed Biotechnol. 2018;46(sup1):926-937. doi: 10.1080/21691401.2018.1439838. Epub 2018 Feb 19.
Doxorubicin is widely used anticancer drug; however, use of doxorubicin is limited. Under externally applied magnetic field, magnetic agents can help to transport drug directly to tumor. Folate receptor is overexpressed in ovarian carcinomas. In this study, we aimed to develop magnetically responsive and folate receptor-targeted biomimetic drug delivery system for ovarian cancer therapy. Doxorubicin-loaded and glucose/gluconic acid-coated magnetic nanoparticles were synthesized and erythrocyte membrane vesicles were used for coating of nanoparticles. Folate ligand was anchored to surface so as to target receptor. Hydrodynamic size of nanocarrier was found as 91.2 ± 20.8 nm. The results showed that delivery system has controlled drug release profile and biocompatible features. In folate-free medium, folate receptor-targeted nanocarrier showed 10.33-fold lower IC values for A2780 cells and 3.93-fold lower for OVCAR3 cells compared to non-targeted nanoparticles and demonstrated more cytotoxicity against ovarian cancer cells. Moreover, magnetically and folate receptor-targeted doxorubicin delivery system was significantly more effective for therapy of xenografted nude mice than free doxorubicin based on tumor shrinkages and biochemical parameters. In conclusion, it can be suggested that folate ligand-attached and biomimetically designed magnetic drug delivery system have advantages and potential for targeted ovarian cancer therapy.
多柔比星是一种广泛应用的抗癌药物;然而,多柔比星的使用受到限制。在外部施加的磁场下,磁性剂可以帮助将药物直接输送到肿瘤部位。叶酸受体在卵巢癌中过度表达。在这项研究中,我们旨在开发磁响应和叶酸受体靶向仿生药物传递系统用于卵巢癌治疗。载多柔比星和葡萄糖/葡萄糖酸涂层的磁性纳米粒子被合成,并使用红细胞膜囊泡来包裹纳米粒子。叶酸配体被锚定在表面以靶向受体。纳米载体的水动力粒径被发现为 91.2±20.8nm。结果表明,该递药系统具有控制药物释放的特点和生物相容性。在无叶酸培养基中,叶酸受体靶向纳米载体对 A2780 细胞的 IC 值比非靶向纳米载体低 10.33 倍,对 OVCAR3 细胞的 IC 值低 3.93 倍,对卵巢癌细胞表现出更强的细胞毒性。此外,与游离多柔比星相比,基于肿瘤缩小和生化参数,磁靶向和叶酸受体靶向多柔比星递药系统对异种移植裸鼠的治疗效果显著更好。总之,可以认为叶酸配体修饰和仿生设计的磁性药物传递系统具有用于靶向卵巢癌治疗的优势和潜力。