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Abstract

A novel pH-responsive nanomicelle (QT-CA-CS) based on Chitosan, Quercetin and Citraconic anhydride was reported in this study. The QT-CA-CS could self-assemble into nanomicelles for encapsulating anticancer drug doxorubicin (DOX) by ultrasound. The novel nanomicelles had P-gp inhibition and pH responsiveness, which was capable of inhibiting drug efflux and responding to an endo/lysosomal acidic environment. The drug loaded nanomicelles had high encapsulation rate (more than 80%), small particle size (133.52 ± 4.13 nm) and positive zeta potential (+13.5 mV). The release rate of doxorubicin and quercetin in pH 4.5 was faster than that in pH 7.4. QT-CA-CS-DOX nanomicelles could promote cellular uptake of doxorubicin by drug resistance cell line (MCF-7/ADR), which was 8.62 folds higher than that of free doxorubicin. Most importantly, QT-CA-CS-DOX nanomicelles could escape from lysosomes and rapidly release doxorubicin and quercetin in the cytoplasm, which had an enhanced inhibitory effect on tumor cells, especially for MCF-7/ADR. The above results proved that the high potential of QT-CA-CS-DOX nanomicelles for multidrug resistance related tumor therapy.