The potential of pH-responsive PEG-hyperbranched polyacylhydrazone micelles for cancer therapy.
The potential of pH-responsive PEG-hyperbranched polyacylhydrazone micelles for cancer therapy.
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DOI：
10.1016/j.biomaterials.2013.12.074
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发表时间：
2014-03
期刊：
影响因子：
14
通讯作者：
Jingshuang Yu;Hongping Deng;F. Xie;Wantao Chen;Bangshang Zhu;Qin Xu
中科院分区：
文献类型：
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作者：
Jingshuang Yu;Hongping Deng;F. Xie;Wantao Chen;Bangshang Zhu;Qin Xu
pH响应性超支化聚合物因其在肿瘤靶向药物输送方面的独特性能而引起了人们的广泛关注。本研究中，我们描述了一种pH响应性药物载体，聚乙二醇（PEG）-超支化聚酰腙（HPAH），它可以形成纳米胶束，用于pH控制药物释放的抗癌药物载体。通过核磁共振谱（NMR）和傅里叶变换红外光谱（FTIR）对PEG-HPAH的分子结构进行了表征。使用针对pH为8.0的PBS的透析方法制备直径约为190 nm的载药胶束。载药胶束显示出所需的pH依赖性药物释放特性。药物释放水平在中性和碱性pH下较低，但随着介质pH的降低而显著增加。细胞内摄取结果表明，PEG-HPAH-药物胶束可以有效地将化疗药物输送到细胞内。此外，发现载药胶束的亚细胞定位不同于游离药物，其中载药胶束主要位于细胞质中。多西紫杉醇（DTX）PEG-HPAH胶束对肿瘤细胞具有较强的体外杀伤活性。当与葡萄糖联合给药时，PEG-HPAH-DTX胶束显示出上级的抗肿瘤效果和较低的全身毒性。生物分布曲线显示胶束处理组中肿瘤组织和血浆中的累积药物水平增加。结果表明，PEG-HPAH-DTX纳米胶束可作为一种选择性肿瘤靶向给药系统。
pH-responsive hyperbranched polymers have attracted much attention due to their unique properties for tumor-targeted drug delivery. In this study, we describe a pH-responsive drug carrier, poly (ethylene glycol) (PEG)-hyperbranched polyacylhydrazone (HPAH), which can form nanoscale micelles to be used as anti cancer drug carriers with pH-controlled drug release. The molecular structure of PEG-HPAH was confirmed by nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR). The drug-loaded micelles with a diameter of approximately 190 nm, were prepared using a dialysis method against PBS with a pH of 8.0. The drug-loaded micelles showed the desired pH-dependent drug release properties. The drug release levels were low at neutral and alkaline pH, but increased significantly with a decrease in the pH of the medium. Intracellular uptake results indicated that the PEG-HPAH-drug micelles could efficiently deliver chemotherapeutic drugs into the cells. In addition, it was found that the subcellular localization of the drug-loaded micelles was different from that of free drugs, in which the drug-loaded micelles were mainly in the cytoplasm. The docetaxel (DTX)-loaded PEG-HPAH micelles presented a high cytotoxic activity against tumor cellsin vitro. When combined with the administration of glucose, the PEG-HPAH-DTX micelles exhibited a superior anti-tumor efficacy and a lower systemic toxicityin vivo. The biodistribution profile showed increased accumulated drug levels in tumor tissue and plasma in micelles treated group. The results indicate that the nanoscale PEG-HPAH-DTX micelles may serve as a selective tumor-targeting drug delivery system.