Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe(3+) at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe(3+) was adsorbed in PDA NPs at pH values close to which Fe(OH)(3) begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe(3+). Otherwise, it was demonstrated that Fe(3+) could be released in the late endo/lysosomes thanks to their acidic pH and their Ca(2+) content, and that when Fe(3+) was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe(3+) and doxorubicin may constitute a good approach to target breast tumors.