Two-component reduction-sensitive lipid–polymer hybrid nanoparticles for triggered drug release and enhanced in vitro and in vivo anti-tumor efficacy. (14th November 2016)

• Record Type: Journal Article
• Authors: Zhang, Liu-Jie; Wu, Bo; Zhou, Wei; Wang, Cai-Xia; Wang, Qian; Yu, Hui; Zhuo, Ren-Xi; Liu, Zhi-Lan; Huang, Shi-Wen
• Is Part Of: Biomaterials science. Volume 5:Number 1(2017:Jan.)
• Page Start: 98
• Page End: 110
• Publication Date: 2016-11-14
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c6bm00662k
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Two-component reduction-sensitive lipid–polymer hybrid nanoparticles composed of DLPE-S-S-MPEG and PCL were developed for intracellular reduction triggered delivery of DOX. Abstract : An amphiphilic polymer DLPE-S-S-MPEG was synthesized and employed with PCL to prepare two-component reduction-sensitive lipid–polymer hybrid nanoparticles (SLPNPs) for in vitro and in vivo delivery of a hydrophobic anticancer drug (Doxorubicin, DOX). Insensitive lipid–polymer hybrid nanoparticles (ILPNPs) were prepared as a control. The mean sizes of the LPNPs ranged from 100 nm to 120 nm. The TEM observations showed that the LPNPs have spherical morphologies with homogeneous distribution. The disulfide bond of DLPE-S-S-MPEG was cleaved by dithiothreitol (DTT), which resulted in the disassembly of SLPNPs and triggered the release of encapsulated DOX. The in vitro cytotoxicities of DOX/LPNPs against HeLa cells, HepG2 cells and COS-7 cells were studied. It was demonstrated that DOX/SLPNPs showed higher cytotoxicity against HeLa cells and HepG2 cells than DOX/ILPNPs, but showed a slight difference in the case of COS-7 cells. CLSM observation and FCM measurement further confirmed that the introduction of S–S bonds caused fast intracellular release of DOX from SLPNPs. Moreover, compared with DOX/ILPNPs and free DOX, DOX/SLPNPs exhibited higher antitumor activity. Both DOX/SLPNPs and DOX/ILPNPs showed lower cardiac toxicity and kidney toxicity than free DOX, which were confirmed by histological and immunohistochemical analyses. The tissue distribution of DOX in mice exhibited that two kinds of DOX/LPNPs accumulated extensively in the liver and spleen, while free DOX accumulated mainly in the heart and kidney 12 h after injection. Two-component SLPNPs may be a promising drug delivery carrier for reduction-triggered delivery of DOX.