负载琥珀酸美托洛尔的pH响应性主客体纳米系统抑制乳腺癌肺转移。
A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer.
作者信息
Dan Zhaoling, Cao Haiqiang, He Xinyu, Zhang Zhiwen, Zou Lili, Zeng Lijuan, Xu Yan, Yin Qi, Xu Minghua, Zhong Dafang, Yu Haijun, Shen Qi, Zhang Pengcheng, Li Yaping
机构信息
1. State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.; 2. School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China.
1. State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
出版信息
Theranostics. 2016 Jan 25;6(3):435-45. doi: 10.7150/thno.13896. eCollection 2016.
Cancer metastasis is the leading reason for the high mortality of breast cancer. Herein, we report on a pH-responsive host-guest nanosystem of succinobucol (PHN) with pH-stimuli controlled drug release behavior to improve the therapeutic efficacy on lung metastasis of breast cancer. PHN was composed of the host polymer of β-cyclodextrin linked with multiple arms of N,N-diisopropylethylenediamine (βCD-DPA), the guest polymer of adamantyl end-capped methoxy poly(ethylene glycol) (mPEG-Ad), and the active agent of succinobucol. PHN comprises nanometer-sized homogenous spherical particles, and exhibits specific and rapid drug release in response to the intracellular acidic pH-stimuli. Then, the anti-metastatic efficacy of PHN is measured in metastatic 4T1 breast cancer cells, which effectively confirms the superior inhibitory effects on cell migration and invasion activities, VCAM-1 expression and cell-cell binding of RAW 264.7 to 4T1 cells. Moreover, PHN can be specifically delivered to the sites of metastatic nodules in lungs, and result in an obviously improved therapeutic efficacy on lung metastasis of breast cancer. Thereby, the pH-responsive host-guest nanosystem can be a promising drug delivery platform for effective treatment of cancer metastasis.
癌症转移是乳腺癌死亡率高的主要原因。在此，我们报道了一种具有pH刺激控制药物释放行为的琥珀酸布可的pH响应主客体纳米系统（PHN），以提高对乳腺癌肺转移的治疗效果。PHN由与N，N-二异丙基乙二胺多臂连接的β-环糊精主体聚合物（βCD-DPA）、金刚烷基封端的甲氧基聚（乙二醇）客体聚合物（mPEG-Ad）和琥珀酸布可活性剂组成。PHN由纳米级均匀球形颗粒组成，并在细胞内酸性pH刺激下表现出特异性和快速的药物释放。然后，在转移性4T1乳腺癌细胞中测量PHN的抗转移效果，这有效地证实了其对RAW 264.7与4T1细胞的细胞迁移和侵袭活动、VCAM-1表达以及细胞间结合的优异抑制作用。此外，PHN可以特异性地递送至肺转移结节部位，并对乳腺癌肺转移产生明显改善的治疗效果。因此，pH响应主客体纳米系统有望成为有效治疗癌症转移的药物递送平台。
Zotero 插件