A pH-sensitive drug delivery system based on hyaluronic acid co-deliver doxorubicin and aminoferrocene for the combined application of chemotherapy and chemodynamic therapy

Doxorubicin is a broad-spectrum antineoplastic drug used in tumor therapy, its clinical application is limited by side effects on normal tissues. In this article, a pH-responsive drug delivery system (NPs(DOX/AFc)) with codelivers doxorubicin (DOX) and aminoferrocene (AFc) was prepared by a two-step synthesis method including the oxidation of hyaluronic acid and Schiff base reaction. NPs(DOX/AFc) can be used in combination therapy of chemodynamic therapy (CDT) and chemotherapy (CT), thus the dosage of the chemotherapeutic drug DOX was reduced. The drug release behavior of NPs(DOX/AFc) in vitro showed that acid-responsive drug releases under the endosomal/lysosomal environment were 56.5 % of DOX and 61.8 % of AFc. In vitro toxicity experiments showed that DOX and AFc had synergistic effects (CI = 0.878). The results of intracellular ROS measurement and the mitochondrial membrane potential analysis showed that in tumor cells NPs(DOX4/AFc) induced more production of reactive oxygen species and more loss of the mitochondrial membrane potential. In short, this codelivery system based on polymer prodrugs provides a new idea for the combined application of CT and CDT.

Automated summary

A pH-responsive drug delivery system (NPs(DOX/AFc)) was developed for codelivery of doxorubicin (DOX) and aminoferrocene (AFc) in tumor therapy, showing reduced dosage of DOX and potential synergistic effects between DOX and AFc. The system demonstrated increased generation of reactive oxygen species and loss of mitochondrial membrane potential in tumor cells, providing a new approach for combined application of chemotherapy (CT) and chemodynamic therapy (CDT).