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

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 203; p. 111750
• Main Authors: Lei, Mengheng, Chen, Gang, Zhang, Mengyao, Lei, Jiaqing, Li, Tingting, Li, Dan, Zheng, Hua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2021
• Subjects: Chemodynamic therapy; Combination therapy; Fenton; Hyaluronic acid; Reactive oxygen species; Fenton; Reactive oxygen species; Chemodynamic therapy; Combination therapy; Hyaluronic acid
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2021.111750

[Display omitted] •NPs(DOX/AFc) were prepared by a two-step synthesis method.•Doxorubicin and aminoferrocene were co-loaded in NPs(DOX/AFc).•NPs(DOX/AFc) were designed for combination therapy of chemotherapy and chemodynamic therapy.•NPs(DOX/AFc) were tumor-targeting and pH-sensitive. 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 co-delivers 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 co-delivery system based on polymer prodrugs provides a new idea for the combined application of CT and CDT.