Journal
JOURNAL OF COLLOID AND INTERFACE SCIENCE
Volume 472, Issue -, Pages 90-98Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2016.03.039
Keywords
pH-sensitive; Co-delivery system; Active targeting; Multidrug resistance reversal; Enhanced cancer therapy
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Funding
- National Natural Science Foundation of China (NSFC) [21373126]
- Natural Science Foundation for Distinguished Young Scholars of Shandong Province [JQ201303]
- China-Australia Centre for Health Sciences Research (CACHSR)
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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)
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