Theranostics 2016; 6(3):435-445. doi:10.7150/thno.13896

Research Paper

A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer

Zhaoling Dan1,2,#, Haiqiang Cao1,#, Xinyu He1, Zhiwen Zhang1,✉, Lili Zou2, Lijuan Zeng3, Yan Xu2, Qi Yin1, Minghua Xu1, Dafang Zhong1, Haijun Yu1, Qi Shen2, Pengcheng Zhang1, Yaping Li1,✉

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
3. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
#These authors contributed equally.

Abstract

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.

Keywords: Host-guest nanosystem, pH-responsive, Cyclodextrin, Cancer metastasis, Breast cancer.

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How to cite this article:
Dan Z, Cao H, He X, Zhang Z, Zou L, Zeng L, Xu Y, Yin Q, Xu M, Zhong D, Yu H, Shen Q, Zhang P, Li Y. A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer. Theranostics 2016; 6(3):435-445. doi:10.7150/thno.13896. Available from http://www.thno.org/v06p0435.htm