Biomimic colloidal self-assembly of epirubicin/ferric ion multi-enzyme delivery for synergistic photothermal therapy of metastatic triple-negative breast cancer.

An increased breast cancer metastatic rate is the principal cause of poor prognosis, wherein the inflammatory environment of the tumor tissue intensifies metastasis. Although photothermal therapy (PTT) demonstrates remarkable anticancer efficacy, the elevation of inflammation-induced reactive oxygen species (ROS) during PTT exacerbates cancer dissemination. To impede breast tumor metastasis and mitigate inflammation-induced reactive oxygen species (ROS) production during PTT, a colloidal, self-assembled PEF nanodrug (ND) consisting of polyvinylpyrrolidone (PVP), epirubicin (EPI), and iron ions (Fe) was engineered that exhibited anti-inflammatory and PTT properties to reduce the growth of metastatic and primary breast tumors. The designed PEF NDs were spherical (40 nm) and exhibited an efficient light-to-heat conversion. The PEF NDs displayed multiple enzyme-like activities (peroxidase, catalase, and glutathione peroxidase) and efficient photothermal performance. PEF NDs demonstrated a robust correlation between ROS scavenging and photothermal heating, consequently promoting constant ROS consumption during PTT. Due to their intrinsic photothermal properties, PEF NDs successfully suppressed MDA-MB-231 proliferation in primary and metastatic breast tumors via integrated anti-inflammatory actions, as established by TUNEL, Ki-67, and matrix metalloproteinase-9 (MMP-9) staining. PEF NDs had no detrimental effects on vital organs (heart, kidney, liver, lung, or spleen), indicating acceptable in vivo biosafety. Self-assembled nanodrugs with simultaneous photothermal and anti-inflammatory properties have considerable clinical potential in the treatment of metastatic malignancies.