Synergistic breast tumor cell killing achieved by intracellular co-delivery of doxorubicin and disulfiram via core–shell–corona nanoparticles. (29th May 2018)

• Record Type: Journal Article
• Authors: Tao, Xiaoguang; Gou, Jingxin; Zhang, Qianying; Tan, Xinyi; Ren, Tianyang; Yao, Qing; Tian, Bin; Kou, Longfa; Zhang, Ling; Tang, Xing
• Is Part Of: Biomaterials science. Volume 6:Number 7(2018)
• Page Start: 1869
• Page End: 1881
• Publication Date: 2018-05-29
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c8bm00271a
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Core–shell–corona nanoparticles for co-delivery of hydrophilic doxorubicin and hydrophobic disulfiram. Abstract : Combination therapy with different functional chemotherapeutic agents based on nano-drug delivery systems is an effective strategy for the treatment of breast cancer. However, co-delivery of drug molecules with different physicochemical properties still remains a challenge. In this study, an amphiphilic poly (ε-caprolactone)- b -poly (l -glutamic acid)- g -methoxy poly (ethylene glycol) (PCL- b -PGlu- g -mPEG) copolymer was designed and synthesized to develop a nanocarrier for the co-delivery of hydrophilic doxorubicin (DOX) and hydrophobic disulfiram (DSF). The amphiphilic copolymer self-assembled into core–shell–corona structured nanoparticles with the hydrophobic PCL core for DSF loading (hydrophobic interaction) and anionic poly (glutamic acid) shell for DOX loading (electrostatic interaction). DSF and DOX co-loaded nanoparticles (Co-NPs) resulted in high drug loading and precisely controlled DSF/DOX ratio via formulation optimization. Compared with free drug solutions, DSF and DOX delivered by the Co-NPs were found to have improved intracellular accumulation. Results of cytotoxicity assays showed that DSF/DOX delivered at the weight ratio of 0.5 and 1 could achieve a synergistic cytotoxic effect on breast cancer cell lines (MCF-7 and MDA-MB-231). In vivo imaging confirmed that the core–shell–corona nanoparticles could efficiently accumulate in tumors. In vivo anti-tumor effect results indicated that Co-NPs showed an improved drug synergistic effect on antitumor activity compared with the free drug combination. Therefore, it can be concluded that core–shell–corona nanoparticles prepared by PCL- b -PGlu- g -mPEG could be a promising co-delivery system for drug combination therapy in the treatment of breast cancer.