Department of Oncology, Nanjing Drum Tower Hospital, Nanjing University of Traditional Chinese Medicine, Nanjing 210008, Jiangsu, China.
J Biomed Nanotechnol. 2013 Aug;9(8):1354-61. doi: 10.1166/jbn.2013.1631.
Nanoscale particles, as drug carriers, have a potential to improve drug therapeutic efficiency. However, the feasible design of the nanostructure containing chemotherapeutic agents and the behavior of the delivery to tumor tissues and cells has not been adequately investigated. In this study, we developed a novel nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL)-based structure for tumor-targeted EVO (an alkaloid isolated from Evodia rutaecarpa) delivery. We found that EVO-NPs were transformed by gelatinases, which could significantly promote drug release and enhance the cellular uptake of EVO (P < 0.01). In vivo biodistribution study demonstrated that targeted EVO-NPs could accumulate and remain in the tumor regions. Moreover, EVO-NPs exhibited higher tumor growth suppression than EVO on hepatic H22 tumor model via intravenous administration (P < 0.01). Both in vitro and in vivo experiments suggested that the gelatinase-mediated nanoscale delivery system was promising for improvement of antitumor efficacy in various over-expressed gelatinase cancers.
纳米颗粒作为药物载体,具有提高药物治疗效果的潜力。然而,对于包含化疗药物的纳米结构的可行设计以及递送至肿瘤组织和细胞的行为,尚未进行充分的研究。在本研究中,我们开发了一种新型纳米颗粒,由明胶酶切割肽与聚乙二醇(PEG)和聚己内酯(PCL)基结构组成,用于肿瘤靶向 EVO(从吴茱萸中分离得到的一种生物碱)的递送。我们发现 EVO-NPs 可被明胶酶转化,这可显著促进药物释放并增强 EVO 的细胞摄取(P < 0.01)。体内分布研究表明,靶向 EVO-NPs 可在肿瘤区域聚集并保持。此外,通过静脉注射,EVO-NPs 在肝 H22 肿瘤模型中表现出比 EVO 更高的肿瘤生长抑制作用(P < 0.01)。体外和体内实验均表明,明胶酶介导的纳米递药系统有望提高各种过度表达明胶酶的癌症的抗肿瘤疗效。