Tumor-Homing Cell-Penetrating Peptide Linked to Colloidal Mesoporous Silica Encapsulated (-)-Epigallocatechin-3-gallate as Drug Delivery System for Breast Cancer Therapy in Vivo
Tumor-Homing Cell-Penetrating Peptide Linked to Colloidal Mesoporous Silica Encapsulated (-)-Epigallocatechin-3-gallate as Drug Delivery System for Breast Cancer Therapy in Vivo
复制标题
肿瘤归巢细胞穿透肽连接到胶体介孔二氧化硅封装的 (-)-表没食子儿茶素-3-没食子酸酯作为体内乳腺癌治疗的药物递送系统
DOI：
10.1021/acsami.5b05618
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发表时间：
2015-08-19
影响因子：
9.5
通讯作者：
He, Zhiwei
中科院分区：
文献类型：
--
作者：
Ding, Jie;Yao, Jing;He, Zhiwei
化疗是使用化学药物来防止癌细胞增殖、侵袭和转移，但一个严重的障碍是化疗药物不仅打击癌细胞，而且还打击正常细胞。因此，应开发和提取无副作用的抗癌药物。（-）-表没食子儿茶素没食子酸酯（EGCG）是绿色茶的主要成分，具有良好的药用价值，如抗癌作用、DNA保护作用等。在这里，我们报告了一个药物输送系统（DDS）装载表没食子儿茶素没食子酸酯，以提高其稳定性，有前途的目标和抗癌作用，在体外和体内。所设计的DDS由三个主要部分组成：抗癌药物表没食子儿茶素没食子酸酯（EGCG）;药物载体介孔硅胶（CMS）;靶向配体乳腺肿瘤归巢细胞穿透肽（PEGA-pVEC肽）。基于CCK-8测定、共聚焦成像、细胞周期分析和Western印迹的结果，通过将EGCG负载到CMS和CMS@肽中，增强了EGCG的抗癌作用。体内实验表明CMS对荷瘤小鼠的抑瘤作用不明显，但CMS@peptide@EGCG的抑瘤率最高，达89.66%。器官H&E染色显示所有实验组均无组织损伤。以上结果表明，EGCG是一种优良的抗癌药物，无副作用，CMS@肽通过靶向蓄积和释放，可显著提高EGCG对乳腺肿瘤的疗效，为CMS@肽作为DDS的靶向载体提供了有力的证据。
Chemotherapy is the use of chemical drugs to prevent cancer cell proliferation, invasion, and metastasis, but a serious obstacle is that chemotherapeutics strikes not only on cancerous cells, but also on normal cells. Thus, anticancer drugs without side effects should be developed and extracted. (-)-Epigallocatechin-3-gallate (EGCG), a major ingredient of green tea, possesses excellent medicinal values, such as anticancer effects, DNA-protective effects, etc. However, EGCG will be mostly metabolized if it is directly orally ingested. Here, we report a drug delivery system (DDS) for loading EGCG to enhance its stability, promising target and anticancer effects in vitro and in vivo. The designed DDS is composed of three main moieties: anticancer drug, EGCG; drug vector, colloidal mesoporous silica (CMS); target ligand, breast tumor-homing cell-penetrating peptide (PEGA-pVEC peptide). Based on the results of CCK-8 assay, confocal imaging, cell cycle analysis, and Western blot, the anticancer effect of EGCG was increased by loading of EGCG into CMS and CMS@peptide. In vivo treatment displayed that CMS had a not obvious influence on breast tumor bearing mice, but CMS@peptide@EGCG showed the greatest tumor inhibition rate, with about 89.66%. H&E staining of organs showed no tissue injury in all experimental groups. All the above results prove that EGCG is an excellent anticancer drug without side effects and CMS@peptide could greatly promote the efficacy of EGCG on breast tumors by targeted accumulation and release, which provide much evidence for the CMS@peptide as a promising and targeting vector for DDS.