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Tumor-Cell-Surface Adherable Peptide-Drug Conjugate Prodrug Nanoparticles Inhibit Tumor Metastasis and Augment Treatment Efficacy.
Nano Letters ( IF 9.6 ) Pub Date : 2020-05-28 , DOI: 10.1021/acs.nanolett.0c00152 Chen Qian 1 , Jingjing Wang 1 , Ying Qian 1 , Rongfeng Hu 2 , Jiayu Zou 1 , Chenqi Zhu 1, 3 , Yuan Zhu 1 , Shuyang Qi 1 , Xiaobin Jia 4 , Li Wu 1 , Weidong Li 1 , Zhipeng Chen 1
Nano Letters ( IF 9.6 ) Pub Date : 2020-05-28 , DOI: 10.1021/acs.nanolett.0c00152 Chen Qian 1 , Jingjing Wang 1 , Ying Qian 1 , Rongfeng Hu 2 , Jiayu Zou 1 , Chenqi Zhu 1, 3 , Yuan Zhu 1 , Shuyang Qi 1 , Xiaobin Jia 4 , Li Wu 1 , Weidong Li 1 , Zhipeng Chen 1
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Cancer metastasis is the main cause of chemotherapeutic failure. Inhibiting the activity of matrix metalloproteinases (MMPs) is a common strategy for reducing metastasis. However, broad-spectrum MMP-inhibitors (MMPI) may cause undesired side effects. Here, we screened a selective MMP2 inhibitor (CCKIGLFRWR) and linked it with doxorubicin (DOX) to produce an amphiphilic peptide-drug conjugate (PDC). Then novel core–shell nanoparticles were self-assembled from PDC core and modified polylysine (MPL) shell. When the particles were passively targeted to the tumor site, the PDC core was exposed for charge switch of the MPL shell, aggregated for its transformation behavior, and specially adhered to the cell membrane. The disulfide bond between the MMPI peptide and DOX was broken via a low concentration of glutathione-mediated reduction in tumor microenvironment. DOX could effectively enter the tumor cells. Meanwhile, the MMPI peptide could selectively inhibit the activity of the MMP2 and effectively inhibit tumor metastasis.
中文翻译：
肿瘤细胞表面粘附肽-药物共轭前药纳米颗粒抑制肿瘤转移和增强治疗功效。
癌症转移是化疗失败的主要原因。抑制基质金属蛋白酶（MMPs）的活性是减少转移的常见策略。但是，广谱MMP抑制剂（MMPI）可能会导致不良的副作用。在这里，我们筛选了一种选择性MMP2抑制剂（CCKIGLFRWR），并将其与阿霉素（DOX）连接以产生两亲性肽-药物偶联物（PDC）。然后从PDC核和修饰的聚赖氨酸（MPL）壳中自动组装新型核-壳纳米颗粒。当将粒子被动地靶向肿瘤部位时，PDC核心暴露出来以进行MPL壳的电荷转换，聚集其转化行为，并特别粘附在细胞膜上。MMPI肽和DOX之间的二硫键通过低浓度的谷胱甘肽介导的肿瘤微环境还原而断裂。DOX可以有效进入肿瘤细胞。同时，MMPI肽可以选择性抑制MMP2的活性，并有效抑制肿瘤转移。
更新日期：2020-05-28
中文翻译：
肿瘤细胞表面粘附肽-药物共轭前药纳米颗粒抑制肿瘤转移和增强治疗功效。
癌症转移是化疗失败的主要原因。抑制基质金属蛋白酶（MMPs）的活性是减少转移的常见策略。但是，广谱MMP抑制剂（MMPI）可能会导致不良的副作用。在这里，我们筛选了一种选择性MMP2抑制剂（CCKIGLFRWR），并将其与阿霉素（DOX）连接以产生两亲性肽-药物偶联物（PDC）。然后从PDC核和修饰的聚赖氨酸（MPL）壳中自动组装新型核-壳纳米颗粒。当将粒子被动地靶向肿瘤部位时，PDC核心暴露出来以进行MPL壳的电荷转换，聚集其转化行为，并特别粘附在细胞膜上。MMPI肽和DOX之间的二硫键通过低浓度的谷胱甘肽介导的肿瘤微环境还原而断裂。DOX可以有效进入肿瘤细胞。同时，MMPI肽可以选择性抑制MMP2的活性，并有效抑制肿瘤转移。
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