Active targeting co-delivery system based on pH-sensitive methoxy-poly(ethylene glycol)_2K-poly(ε-caprolactone)_4K-poly(glutamic acid)_1K for enhanced cancer therapy

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• 作者：Nuannuan Li^a ; ¹ ; Chunzhi Huang^a ; ¹ ; Yuxia Luan^a ; ^{yuxialuan@sdu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Aixin Song^b ; Yunmei Song^c ; Sanjay Garg^c
• 关键词：pH-sensitive ; Co-delivery system ; Active targeting ; Multidrug resistance reversal ; Enhanced cancer therapy
• 刊名：Journal of Colloid and Interface Science
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：472
• 期：Complete
• 页码：90-98
• 全文大小：1833 K

文摘

In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol)_2K-poly(ε-caprolactone)_4K-poly(glutamic acid)_1K (mPEG_2K-PCL_4K-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-PCL_4K-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) 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.