Enhancement of radiotherapy efficacy by docetaxel-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer
Enhancement of radiotherapy efficacy by docetaxel-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer
复制标题
负载多西紫杉醇的明胶酶刺激 PEG-Pep-PCL 纳米颗粒增强胃癌放疗效果。
DOI：
10.1016/j.canlet.2013.12.002
复制
发表时间：
2014-04-28
期刊：
影响因子：
9.7
通讯作者：
Liu, Bao-Rui
中科院分区：
文献类型：
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作者：
Cui, Fang-bo;Li, Ru-Tian;Liu, Bao-Rui
多西他赛（DOC）作为放射增敏剂广泛应用于包括胃癌（GC）在内的多种肿瘤，但其治疗效果仍有待提高。在这项研究中，使用基于明胶酶刺激策略的紫杉醇纳米粒（DOC-NPs），我们比较了它们与多西他赛在GC中的放射增强效果。与DOC相比，DOC-NPs在明胶酶过表达的胃癌细胞中的放射增敏作用显著增强（增敏比增加1.09 ~ 1.24倍，P < 0.01），而在明胶酶缺乏的正常胃粘膜细胞中增敏作用略有增加（1.02倍，P = 0.38）。放射增敏效果的改善与G2/M期阻滞增强、活性氧（ROS）增加、更有效的DSB和促进细胞凋亡有关。更重要的是，通过在异种移植物中静脉内注射，DOC-NP（估计为“非常活性”）的放射增敏功效比DOC（估计为“中等活性”）更突出。总之，DOC-NP是明胶酶过度表达肿瘤的高度选择性放射增敏剂，并且比DOC更有效。明胶酶介导的纳米级给药系统通过改变肿瘤与正常组织之间共同的微环境差异，具有普适性和选择性，是一种潜在的放射增敏剂治疗策略。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Docetaxel (DOC) is widely used as radiosensitizer in various tumors, including gastric cancer (GC), but its therapeutic effect remains to be improved. In this study, using docetaxel-loaded nanoparticles (DOC-NPs) based on gelatinase-stimuli strategy, we compared their radioenhancement efficacy with docetaxel in GC. Compared with DOC, radiosensitization of DOC-NPs was improved significantly (sensitization enhancement ratio increased 1.09-fold to 1.24-fold, P < 0.01) in all three gelatinase overexpressing GC cells, while increased slightly (1.02-fold, P = 0.38) in gelatinase deficient normal gastric mucosa cells. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS), more effective DSBs and promoted apoptosis. More importantly, the radiosensitization efficacy of DOC-NPs (estimated as "very active") was more prominent than DOC (estimated as "moderately active") by intravenous injection in xenograft. In conclusion, DOC-NPs are highly selective radiosensitizers in gelatinase over-expressing tumors, and more effective than DOC. By manipulating the common microenvironment difference between tumor and normal tissue, gelatinase-mediated nanoscale delivery system serves as a potential strategy possessing both universality and selectivity for radiosensitizers. (C) 2013 Elsevier Ireland Ltd. All rights reserved.