Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.
Site-Specific Drug-Releasing Polypeptide Nanocarriers Based on Dual-pH Response for Enhanced Therapeutic Efficacy against Drug-Resistant Tumors.
复制标题
基于双pH响应的位点特异性释药多肽纳米载体增强耐药肿瘤的治疗效果
DOI：
10.7150/thno.11821
复制
发表时间：
2015
期刊：
影响因子：
12.4
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Dong Y;Yang J;Liu H;Wang T;Tang S;Zhang J;Zhang X
为了增强耐药肿瘤中的有效药物蓄积，（PEG-Phis/Pasp-DOX/CA 4）系统可响应肿瘤细胞外和细胞内pH。该系统可首先释放包埋的肿瘤血管抑制剂（CA 4）以瞬时“正常化”血管并促进药物有效地内化至肿瘤，然后引发第二次pH响应以使缀合的活性抗癌药物（DOX）在肿瘤细胞中游离。将包封系统（PEG-Phis/DOX/CA 4）（CA 4和DOX均包埋在纳米颗粒中）用作对照。与PEG-Phis/DOX/CA 4相比，PEG-Phis/Pasp-DOX/CA 4对阿霉素敏感和耐药细胞（MCF-7和MCF-7/ADR）的细胞毒作用增强。此外，PEG-Phis/Pasp-DOX/CA 4导致耐药性肿瘤的治疗功效增强，毒性降低。这些结果表明，这种位点特异性药物释放系统可以作为重复给药的癌症治疗方法。
To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasculature and facilitate drug internalization to tumors efficiently, and then initiate the secondary pH-response to set the conjugated active anticancer drug (DOX) free in tumor cells. The encapsulated system (PEG-Phis/DOX/CA4), both CA4 and DOX embedding in the nanoparticles, was used as a control. Comparing with PEG-Phis/DOX/CA4, PEG-Phis/Pasp-DOX/CA4 exhibited enhanced cytotoxicity against DOX-sensitive and DOX-resistant cells (MCF-7 and MCF-7/ADR). Moreover, PEG-Phis/Pasp-DOX/CA4 resulted in enhanced therapeutic efficacy in drug-resistant tumors with reduced toxicity. These results suggested that this site-specific drug-releasing system could be exploited as a promising treatment for cancers with repeated administration.