Active targeting co-delivery system based on pH-sensitive methoxy-poly (ethylene glycol)(2K)-poly(epsilon-caprolactone)(4K)-poly(glutamic acid)(1K) for enhanced cancer therapy

作者：Li, Nuannuan; Huang, Chunzhi; Luan, Yuxia^*; Song, Aixin; Song, Yunmei; Garg, Sanjay

来源：Journal of Colloid and Interface Science, 2016, 472: 90-98.

DOI：10.1016/j.jcis.2016.03.039

• pH-sensitive
• Co-delivery system
• Active targeting
• Multidrug resistance reversal
• Enhanced cancer therapy

In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly (ethylene glycol)(2K)-poly(epsilon-caprolactone)(4K)-poly(glutamic acid)(1K) (mPEG(2K)-PCL4K-PGA(1K)-FA), which could form the polymeric assembly in an aqueous solution, for co-delivering hydrophilic drugs doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) (FA-poly(DOX+VER)). Since VER was an effective P-glycoprotein inhibitor, the combination of DOX and VER could reverse the multidrug resistance efficiently and enhance the therapeutic effect. Therefore, the inhibition ratios of MCF-7/ADR resistant cancer cell treated by FA-poly (DOX+VER) were almost more than 30% higher than those of FA-polyDOX after 48 h and 72 h. Furthermore, the conjugation of FA could lead the co-delivery systems actively targeting into the FA receptor over-expressing cancer cells in addition to the passive accumulation of the assembly in tumor tissues. Importantly, the prepared mPEG(2K)-PCL4K-PGA(1K)-FA assembly showed high pH-sensitive property, which made the drugs mostly released in tumor tissue (acid environment) than in physiological environment (neutral environment). In summary, the as-prepared co-delivery system FA-poly(DOX+VER)

• 出版日期2016-6-15
• 单位山东大学