Buffet-style Cu(II) for enhance disulfiram-based cancer therapy

Abstract

Studies have shown that disulfiram (DSF) can combine with Cu²⁺ to form bis(N, N-diethyldithiocarbamate) copper(II) complex (CuET) as antitumor drugs. However, there is insufficient endogenous Cu²⁺ dose to eradicate cancer cells selectively. Inspired by the buffet, we use Cu²⁺ doped hollow zeolitic imidazolate framework nanoparticles (HZIF_Cu) as the carrier and equipped with DSF and indocyanine green (ICG) and targeted by folic acid (FA) (D&I@HZIF_Cu-FA) to enhance DSF-based cancer therapy. D&I@HZIF_Cu-FA could effectively supply Cu²⁺ by a buffet-style, assisting the "DSF-to-CuET" transformation in the tumor. Additionally, self-supply Cu²⁺ could convert H₂O₂ into ·OH by triggering a Fenton-like reaction for chemo-dynamic therapy, and ICG achieves photothermal therapy for tumors under laser irradiation. This work provides a buffet-style for Cu²⁺ to make DSF a strong candidate for cancer treatment by combining chemotherapy, chemo-dynamic therapy, and photothermal therapy and inspires more research about its applications in tumor therapy.

Keywords: Chemo-dynamic therapy; Chemotherapy; Disulfiram; Photothermal therapy.