Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
Department of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
J Nanobiotechnology. 2020 Mar 18;18(1):50. doi: 10.1186/s12951-020-00607-4.
Enzalutamide (Enz) has shown limited bioavailability via oral administration. Castration-resistant prostate cancer (CRPC) is frequent among patients receiving 18-24 months of androgen deprivation therapy. The nonsteroidal anti-androgen enzalutamide (Enz) used in the treatment of prostate cancer has shown limited bioavailability via oral administration. Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for CRPC intravenous treatment, with high drug loading efficiency.
Aminated graphene quantum dots (GQDs) were first cross-linked via disulfide bonds into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study.
The results showed that high drug-loading efficiency was achieved by TP-GQDss via π-π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could inhibit the growth of C4-2B and LNCaP prostate cancer cell lines in vitro. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo.
The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as an intravenous therapy platform for CRPC.
恩扎鲁胺（Enz）经口服给药的生物利用度有限。接受雄激素剥夺治疗 18-24 个月的患者经常发生去势抵抗性前列腺癌（CRPC）。用于治疗前列腺癌的非甾体类抗雄激素恩扎鲁胺（Enz）经口服给药的生物利用度有限。因此，我们开发了一种多功能恩扎鲁胺负载氧化石墨烯纳米系统（TP-GQDss/Enz），用于 CRPC 静脉治疗，具有较高的载药效率。
首先通过二硫键将氨基化石墨烯量子点（GQDs）交联成约 200nm 的石墨烯量子点衍生物（GQDss），然后进一步用肿瘤靶向肽和 PEG 功能化形成 TP-GQDss。将 Enz 载入 TP-GQDss 进行体外和体内研究。
结果表明，TP-GQDss 通过π-π电子相互作用实现了高载药效率。TP-GQDss 可以通过内吞作用被 CRPC 细胞快速内化。此外，TP-GQDss 中的 Enz 可以抑制体外 C4-2B 和 LNCaP 前列腺癌细胞系的生长。此外，TP-GQDss 表现出增强的癌症靶向能力，并减轻了 Enz 的体内副作用。
这里构建的多功能纳米载体可以实现 Enz 的控制释放，并作为 CRPC 的静脉治疗平台。
