aSchool of Biological and Medical Engineering, Hefei University of Technology, Hefei, Anhui 230009, P. R. China.

bDepartment of Aerospace and Mechanical Engineering, Biomedical Engineering IDP, Bio5 Institute, University of Arizona, Tucson, Arizona 85721, USA.

摘要：Due to their clinical use approved by US Food and Drug Administration (FDA), Prussian blue nanoparticles (PB NPs) have been explored as a new generation of photothermal agents for cancer photothermal therapy (PTT). However, PTT treatment alone has limited therapeutic efficiency since it can not eliminate tumor cells compley. Herein we developed a facile method for the synthesis of PB NPs through a combined ligand exchange and thin film hydration process, modified the PB NPs by lipid-PEG conjugation, producing PEGylated PB NPs, and encapsulated doxorubicin (DOX) in the PEGylated PB NPs via hydrophobic interactions, creating PEGylated PB-DOX NPs. Obtained from the results of fluorescence intensity measurements, the loading efficiency and content of DOX in PEGylated PB-DOX NPs was as high as 98.0% and 9.2%, respectively. The DOX release from the PEGylated PB-DOX NPs was significantly enhanced at acidic pH, likely due to the protonation of the amine group, and a three-parameter simulation model was used to gain insight into the pH effect on DOX release. Moreover, a cell cytotoxicity study in vitro shows that PEGylated PB-DOX NPs exhibits a remarkable photothermal-chemo synergistic effect to HeLa cells, attributed to both photothermal ablation mediated by the PEGylated PB NPs and enhanced cellular uptake of DOX. Therefore, our study may open a new path for the production of PB NPs as drug delivery vehicles for combined photothermal-chemo cancer treatment.