标题：Active targeting co-delivery system based on pH-sensitive methoxy-poly(ethylene glycol)2K-poly(Ε-caprolactone)4K-poly(glutamic acid)1Kfor enhanced cancer therapy
作者：Li, Nuannuan ;Huang, Chunzhi ;Luan, Yuxia ;Song, Aixin ;Song, Yunmei ;Garg, Sanjay
作者机构：[Li, Nuannuan ;Huang, Chunzhi ;Luan, Yuxia ] School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province; 250 更多
来源：Journal of Colloid and Interface Science
摘要：In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol)2K-poly(Ε-caprolactone)4K-poly(glutamic acid)1K(mPEG2K-PCL4K-PGA1K-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 mPEG2K-PCL4K-PGA1K-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) demonstrated a high efficiency in reversing the multidrug resistance and targeting FA receptor to improve the anticancer effect of DOX in MCF-7/ADR resistant cells.
© 2016 Elsevier Inc.