Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ɛ-caprolactone) nanoparticles.
Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ɛ-caprolactone) nanoparticles.
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明胶酶刺激策略增强多西紫杉醇负载的聚乙二醇-聚己内酯纳米颗粒的肿瘤递送和治疗效果
DOI：
10.2147/ijn.s26697
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发表时间：
2012
影响因子：
8
通讯作者：
Liu BR
中科院分区：
文献类型：
--
作者：
Liu Q;Li RT;Qian HQ;Yang M;Zhu ZS;Wu W;Qian XP;Yu LX;Jiang XQ;Liu BR
为了提高药物治疗效率，纳米级药物载体得到了广泛的发展。然而，化疗药物对肿瘤组织和细胞的输送并没有得到良好的管理。在这项研究中，我们开发了一种新的“智能”纳米颗粒，由明胶酶裂解肽与聚乙二醇（PEG）和聚己内酯（PCL）为基础的结构组成，用于肿瘤靶向多西紫杉醇递送（DOC-TNPs）。多西他赛负载的PEG-PCL纳米颗粒（DOC-NPs）不显示明胶酶刺激行为作为对照。我们发现明确的证据表明DOC- tnps被明胶酶转化，允许药物释放并增强DOC的细胞摄取（P < 0.01）。体内生物分布研究表明，靶向DOC-TNPs可以在肿瘤区域积累和滞留，而非靶向DOC-NPs可以迅速从肿瘤组织中清除。经静脉给药后，DOC-TNPs对肝脏H22肿瘤模型的抑制作用明显高于已上市的Taxotere®（docetaxel，江苏恒瑞医药公司，中国江苏）和DOC-NPs （P < 0.01）。体外和体内实验表明，明胶酶介导的纳米级递送系统有望提高各种过表达明胶酶癌症的抗肿瘤疗效。
Nanoscale drug carriers have been extensively developed to improve drug therapeutic efficiency. However, delivery of chemotherapeutic agents to tumor tissues and cells has not been favorably managed. In this study, we developed a novel “intelligent” nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(ɛ-caprolactone) (PCL)-based structure for tumor-targeted docetaxel delivery (DOC-TNPs). The docetaxel-loaded PEG-PCL nanoparticles (DOC-NPs) that did not display gelatinase-stimuli behaviors were used as a control. We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01). In vivo biodistribution study demonstrated that targeted DOC-TNPs could accumulate and remain in the tumor regions, whereas non-targeted DOC-NPs rapidly eliminated from the tumor tissues. DOC-TNPs exhibited higher tumor growth suppression than commercialized Taxotere® (docetaxel; Jiangsu Hengrui Medicine Company, Jiangsu, China) and DOC-NPs on hepatic H22 tumor model via intravenous administration (P < 0.01). Both in vitro and in vivo experiments suggest that the gelatinase-mediated nanoscale delivery system is promising for improvement of antitumor efficacy in various overexpressed gelatinase cancers.