Journal
THERANOSTICS
Volume 6, Issue 3, Pages 435-445Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.13896
Keywords
Host-guest nanosystem; pH-responsive; Cyclodextrin; Cancer metastasis; Breast cancer
Categories
Funding
- National Basic Research Program of China [2015CB932103, 2013CB932503]
- National Natural Science Foundation of China [81270047, 81521005]
- K.C. Wong Education Foundation
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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 beta-cyclodextrin linked with multiple arms of N,N-diisopropylethylenediamine (beta CD-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.
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