Phenylboronic Acid-Modified pH/Glucose Dual-Responsive Polymeric Micelles for Targeted Anticancer Drug Delivery

The tumor microenvironment is characterized by several hallmarks such as an acidic pH and high glucose levels in tumor tissues and increased expression of specific proteins and/or sugars on the surface of tumor cells. These unique hallmarks of tumors can be considered in the design of multifunctional drug delivery nanosystems to improve the efficiency of tumor therapy through targeted drug delivery and specific drug release in the tumor tissue. In this study, phenylboronic acid-modified pH- and glucose-responsive polymer micelles were designed for the targeted delivery of anticancer drugs. The polymeric micelles demonstrated prolonged and pH/glucose-triggered drug release and enhanced cellular internalization by B16F10 cells through a receptor-mediated endocytosis pathway. The polymeric micellar system could inhibit the proliferation of B16F10 cells with IC50 values lower than those of unmodified micelles. In addition, the polymeric micellar system could markedly suppress cell migration, colony formation, and invasion and promote the apoptosis of B16F10 cells, indicating good anticancer efficiency in vitro. Therefore, this polymeric nanocarrier provides a potential platform for targeted anticancer therapy.