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

Abstract

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 Fe3+ 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 Fe3+ 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 Fe3+. Otherwise, it was demonstrated that Fe3+ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca2+ content, and that when Fe3+ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe3+ and doxorubicin may constitute a good approach to target breast tumors.

p53 Promotes Ferroptosis in Macrophages Treated with Fe3O4 Nanoparticles

“…Its most important characteristic is the production of ROS, which is mainly caused by dysregulated iron metabolism. Novel nanosystems capable of inducing ferroptosis are being increasingly developed, such as polydopamine NPs and porous yolk-shell Fe (0) NPs . To explore the effects of NPs on macrophages, we sequenced the mRNA of cells exposed to NPs for 24 and 48 h; results show that NPs activated the ferroptosis pathway and upregulated p53 after exposure for 48 h. The tumor suppressor gene p53 plays an essential role in ferroptosis induction by encoding SLC7A11 , the substrate-specific subunit of system Xc–. , It has been reported that p53 promotes ferroptosis in ovarian carcinoma cells .…”

Nature-Inspired Nanoparticles as Paclitaxel Targeted Carrier for the Treatment of HER2-Positive Breast Cancer

“…On one hand, to adsorb both Tmab and PTX, solutions of the antibody (1.35 µM, 17.5 µL) and the drug (0.52 µM, 20.2 µL, 2:1 H 2 O(d)/DMSO) were incorporated to suspensions of PDA NPs (2 mg/mL, 350 µL). The resulting mixtures were kept under orbital shaking (100 rpm) in dark conditions, and loaded PDA NPs were isolated the next day by centrifugation [ 37 ].…”

Multifunctional Nanomaterials for Ferroptotic Cancer Therapy

“…The ferroptosis induced by UPDA-PEG@Fe 2+ NPs was dependent on ROS, whereas UPDA-PEG@Fe 3+ NPs induced LPO-dependent ferroptosis. In another research, DOX was loaded onto the PDA NPs to achieve a synergistic effect ( Nieto et al, 2021 ). The pH determined the Fe 3+ state and the selectivity and therapeutic activity of the resultant Fe 3+ -loaded PDA NPs.…”