Nanoassembly of Probucol Enables Novel Therapeutic Efficacy in the Suppression of Lung Metastasis of Breast Cancer. Issue 22 (16th June 2014)

• Record Type: Journal Article
• Authors: Zhang, Zhiwen; Cao, Haiqiang; Jiang, Shijun; Liu, Zeying; He, Xinyu; Yu, Haijun; Li, Yaping
• Is Part Of: Small. Volume 10:Issue 22(2014:Nov.)
• Page Start: 4735
• Page End: 4745
• Publication Date: 2014-06-16
• Subjects: Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201400799
• Languages: English
• ISSNs: 1613-6810

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Metastasis is one of the major obstacles hindering the success of cancer therapy. The directed nanoassembly of probucol results in the "DNP" system, which greatly improves the oral delivery of probucol and subsequently leads to a novel therapeutic efficacy of probucol in the suppression of lung metastasis of breast cancer. DNP is formed by employing the intermolecular hydrophobic interactions between probucol and polyethylene glycol p‐(1, 1, 3, 3‐tetramethylbutyl)‐phenyl ether (also known as Triton X‐100). After oral administration, the probucol concentration in the intestines is surprisingly about 200 times higher if it is applied as DNP rather than free probucol; it can be absorbed into intestinal enterocytes via clathrin‐mediated endocytosis and transported into the systemic circulation through the lymphatic pathway. Moreover, the oral bioavailability of probucol is significantly higher—13.55 times higher—when applied as DNP in place of free probucol. The drug concentration in major organs is also significantly increased. The in vitro measurements show that the migration and invasion abilities of 4T1 cells are obviously inhibited by DNP. In particular, in an orthotopic metastatic breast cancer model, the notable suppression of lung metastasis from DNP is observed, but no effect is seen from the free‐probucol suspension. As a result, the directed drug nanoassembly may open a new route for enhancing oral drug delivery and enable new therapeutic abilities for probucol against cancer metastasis.</p> </abstract>