Work

Multifunctional DSF-loaded ICG-chelated nanozyme for four-in-one enhanced synergistic tumor therapy

Year: 2025

Type: article

Abstract: Conventional chemotherapy remains a mainstay of cancer treatment but suffers from poor tumor selectivity and severe side effects. Addressing these limitations, we developed an innovative "4-in-1" strategy utilizing Disulfiram (DSF)-loaded Fe-based near-infrared-triggered DMTICH nanozymes integrating synergistic chemotherapy, chemodynamic therapy, photothermal therapy, and photodynamic therapy. DMTICH nanozymes can specifically release DSF and Cu 2+ within the tumor microenvironment, enabling in situ formation of a highly toxic bis ( N , N -diethyldithiocarbamate) copper (II) complex (CuET) to reduce the off-target effects and side effects of Chemotherapy. Notably, DMTICH nanozymes demonstrated triple enzyme-mimicking functions in vitro, including catalase-like, peroxidase-like, and glutathione peroxidase-like activities to efficiently mediate Chemodynamic therapy. These enzymatic functions were significantly reinforced by hyperthermia (Photothermal therapy) under NIR irradiation, thereby boosting total therapeutic efficacy within TME. Furthermore, by chelating Cu 2+ with the hydrophilic domains of ICG to form ICG/Cu (II), DMTICH maintained the enhanced effect on 1 O 2 quantum yield, enabling effective Photodynamic therapy. The potent anticancer capability of DMTICH was also validated in animal studies, where it elevated the tumor site temperature to ∼ 58.3 °C and reduced tumor size to 12.6 % of that in the control group after a complete treatment period. This innovative approach highlights a promising synergistic "4-in-1" strategy, offering a powerful enzymatic platform for multimodal cancer therapies. • An innovative "4-in-1" cancer killing strategy utilizing Disulfiram (DSF)-loaded Fe-based near-infrared-triggered DMTICH was developed. • DMTICH nanozymes demonstrated triple enzyme-mimicking functions in vitro, including catalase-like, peroxidase-like, and glutathione peroxidase-like activities to efficiently mediate CDT. • By chelating Cu 2+ with the hydrophilic domains of ICG to form ICG/Cu (II), DMTICH maintained the enhanced effect on 1 O 2 quantum yield, enabling effective photodynamic therapy. • The potent anticancer capability of DMTICH was validated in animal studies, where it elevated the tumor site temperature to 64.4 °C and reduced tumor size to just 12.6% of that in the control group after treatment. • This innovative approach offers a powerful enzymatic platform for multimodal cancer therapies.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2025.102515