Dual Targeting with Cell Surface Electrical Charge and Folic Acid via Superparamagnetic Fe₃O₄@Cu_2-xS for Photothermal Cancer Cell Killing

A major challenge in cancer therapy is to achieve high cell targeting specificity for the highest therapeutic efficacy. Two major approaches have been shown to be quite effective, namely, (1) bio-marker mediated cell targeting, and (2) electrical charge driven cell binding. The former utilizes the tumor-specific moieties on nano carrier surfaces for active targeting, while the latter relies on nanoparticles binding onto the cancer cell surfaces due to differences in electrical charge. Cancer cells are known for their hallmark metabolic pattern: high rates of glycolysis that lead to negatively charged cell surfaces. In this study, the nanoparticles of Fe₃O₄@Cu_2-xS were rendered positively charged by conjugating their surfaces with different functional groups for strong electrostatic binding onto the negatively-charged cancer cells. In addition to the positively charged surfaces, the Fe₃O₄@Cu_2-xS nanoparticles were also modified with folic acid (FA) for biomarker-based cell targeting. The dual-targeting approach synergistically utilizes the effectiveness of both charge- and biomarker-based cell binding for enhanced cell targeting. Further, these superparamagnetic Fe₃O₄@Cu_2-xS nanoparticles exhibit much stronger IR absorptions compared to Fe₃O₄, therefore much more effective in photothermal therapy.