Novel self-assembled metal-phenolic nanoplatforms for triple-negative breast cancer treatment: photothermal-chemotherapy/ferroptosis synergy inducing immunogenic cell death

Triple-negative breast cancer (TNBC) poses a serious threat to women's health. Currently, chemotherapy remains the first-line treatment in the clinic, and more comprehensive treatments are urgently needed to improve the therapeutic efficacy of TNBC. Emerging studies have indicated that photothermal therapy, ferroptosis and immunotherapy also play crucial roles in TNBC treatment. Iron based metal-phenolic networks (MPNs), an emerging class of nanomaterials, are attracting great attention in tumor related research due to their unique structural features. These features endow MPNs with outstanding catalytic efficiency for the Fenton reaction and excellent metal-ligand conversion properties, offering promising prospects for photothermal and photodynamic therapies as well as combined treatment strategies for tumors. In this study, a novel iron-based metal-phenolic nanoplatform, namely MTO-loaded TA/Fe nanocomposites (MFTA), was synthesized. Mitoxantrone (MTO), a commonly used anthracycline, was employed along with ferric chloride (FeCl3) and tannic acid (TA) in the synthesis process. Firstly, TA and FeCl3, two non-photosensitive substances, underwent a coordination reaction to form a blue-black compound TAF, which exhibited ideal photosensitivity. Secondly, through π-π interactions, TAF and MTO partially quenched the autofluorescence of MTO, leading to a cascade amplification of photothermal conversion in the self-assembled nanoplatforms. The myocardial-protective effect of TA enhanced the safety of MTO-based chemotherapy. Additionally, FeCl3 was partially reduced to ferrous ion (Fe2+) by TA, and the introduction of a large amount of Fe2+ could trigger ferroptosis in TNBC. Moreover, the induction of immunogenic cell death in TNBC cells, which was stimulated by photothermal therapy, chemotherapy and ferroptosis, further enhanced the synergistic effect. Finally, this nanoplatform may help improve real-time photoacoustic imaging and assist in treatment monitoring. In summary, the developed nanoplatform offers a novel strategy for the comprehensive treatment of TNBC, holding certain potential for clinical translation.