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.

中文翻译：

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基于高载药量的多功能氧化石墨烯纳米颗粒的恩杂鲁胺的静脉内递送，用于去势抵抗性前列腺癌治疗

Enzalutamide（Enz）通过口服给药显示出有限的生物利用度。在接受18-24个月雄激素剥夺治疗的患者中，去势抵抗性前列腺癌（CRPC）常见。用于治疗前列腺癌的非甾体类抗雄激素恩杂鲁胺（Enz）已显示出口服限制的生物利用度。因此，我们开发了一种多功能的负载恩杂鲁胺的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。首先将胺化的石墨烯量子点（GQDs）通过二硫键交联到大约200 nm的石墨烯量子点衍生物（GQDss）中，然后再将其与肿瘤靶向肽和PEG官能化以形成TP-GQDss。将Enz装入TP-GQDs中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较高的载药效率。TP-GQDss可以通过内吞作用被CRPC细胞快速内在化。此外，TP-GQDss中的Enz可以在体外抑制C4-2B和LNCaP前列腺癌细胞系的生长。此外，TP-GQDs表现出增强的癌症靶向能力，并减轻了Enz在体内的副作用。此处构建的多功能纳米载体可实现受控的Enz释放，并用作CRPC的静脉治疗平台。TP-GQDs表现出增强的癌症靶向能力，并减轻了Enz在体内的副作用。此处构建的多功能纳米载体可实现受控的Enz释放，并用作CRPC的静脉治疗平台。TP-GQDs表现出增强的癌症靶向能力，并减轻了Enz在体内的副作用。此处构建的多功能纳米载体可实现受控的Enz释放，并用作CRPC的静脉治疗平台。