A pH/ROS dual-responsive nanoparticle system for tumor targeting combined chemotherapy/phototherapy

Abstract

Nanoscale metal–organic framework (nMOF) based nano drug delivery systems show great potential in the biomedical field. In this work, a drug delivery system combined with chemotherapy and phototherapy (DOX/ICG@UiO-66-TK-PEG-F3 or simplified as DI@UiO-TPF3) was designed for the targeted therapy of tumors. The chemotherapeutic drug doxorubicin (DOX) and the photothermal therapeutic agent indocyanine green (ICG) were loaded onto the pH-sensitive UiO-66-NH₂ carrier core by physical adsorption, and the surface of UiO-66-NH₂ was modified by the multifunctional polymer TK-PEG-F3 to improve the stability and targeting of the drug-loaded core. Characterizations show that the drug delivery system DI@UiO-TPF3 was successfully prepared with an excellent drug loading rate (21.6%) and photothermal conversion efficiency (32.92%). DI@UiO-TPF3 not only shows the ability to stimulate a response to release drugs, but also achieves the synergistic anti-tumor effects of chemotherapy and photothermal/photodynamic therapy (PTT/PDT), which was confirmed by in vitro evaluation. In addition, cell experiments have confirmed that DI@UiO-TPF3 connected with F3 peptide can selectively bind to the nucleolin overexpressed on the surface of tumor cells and reduce the toxicity to normal cells. Therefore, DI@UiO-UTPF3 provided a feasible strategy for constructing a targeted drug delivery platform integrating chemotherapy and phototherapy.