One-pot construction of boronate ester based pH-responsive micelle for combined cancer therapy

In this study, one-pot strategy for the construction of micelles loaded with two types of anticancer drugs (i.e., doxorubicin and methotrexate) together is reported. On the basis of the reaction between boronic acid and 1,2-diol to form boronate ester, the formation of amphiphiles, their self-assembly into micelles and drug encapsulation occurs simultaneously under simple dialysis at the appropriate pH condition. In the one-pot strategy, the micelle yield is high (78.2%) and the drug encapsulation efficiency of the two drugs is improved compared with that of the traditional method. The micelles can selectively increase the drug release ratio at acidic pH, showing the pH-responsive behavior inherited from the property of boronate ester. By combining doxorubicin and methotrexate, the half-maximum inhibition concentrations of the two drugs are obviously reduced, showing synergistic efficacy against cancer cells. This strategy is promising and may be expanded to various applications. (C) 2016 Elsevier B.V. All rights reserved.