Iron oxide-based enzyme mimic nanocomposite for dual-modality imaging guided chemical phototherapy and anti-tumor immunity against immune cold triple-negative breast cancer

Abstract Triple-negative breast cancer has few biomarkers to guide benefit from immunotherapy; furthermore, the biochemical features of the tumor microenvironment including acidosis, hypoxia, and high hydrogen peroxide concentrations, significantly modulate cancer cell metabolism and metastatic potential, and associate with bad outcomes from chemo-radiotherapy and surgery. Herein, a theranostic nanocomposite with a dual imaging modality and chemical phototherapeutic capacity has been used for breast cancer cell inhibition, which is developed to self-assemble superparamagnetic iron oxide nanocrystals and IR-780 iodides in one system. Due to the magnetic resonance and near-infrared Ⅱ fluorescence capacity, this nanocomposite serves as a contrast agent for the high-sensitivity, accurate cancer diagnosis and facilitates imaging-guided phototherapy. Furthermore, this nanocomposite not only performs dual enzyme-like activities in the tumor microenvironment, but also carries out the bioeffect of hyperthermia and oxidative stress, which could repolarize tumor-associated macrophages from the tumor-promoting M2 phenotype into the tumoricidal M1 phenotype, reduce the number of immunosuppressive cells, and execute immune activation. Through simultaneous chemical phototherapy and anti-tumor immunity, this iron oxide-based nanocomposite successfully suppresses tumor growth and metastasis, and has good biocompatibility in normal tissues and organs; thus, it might provide new insights into the development of a novel cancer therapy strategy.