Dynamic covalent chemistry-regulated stimuli-activatable drug delivery systems for improved cancer therapy

Drug delivery systems (DDSs) are of paramount importance to deliver drugs at the intended targets, e.g., tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles. However, the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release. Dynamic chemical bonds having stimuli-liable properties are therefore introduced into DDSs for regulating the drug release kinetics. This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy. The review discusses the constitutions of the major classes of dynamic covalent bonds, and the respective applications in the tumor-targeted DDSs which are based on the different responsive mechanisms, including acid-activatable and reduction-activatable. Furthermore, the review also discusses combination strategies of dual dynamic covalent bonds which can response to the complex tumor microenvironment much more accurately, and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.