Highly Stable, Coordinated Polymeric Nanoparticles Loading Copper(II) Diethyldithiocarbamate for Combinational Chemo/Chemodynamic Therapy of Cancer

Abstract

Disulfiram (DSF) has excellent in vitro anticancer activity in the presence of Cu(II). The anticancer mechanism studies have demonstrated that copper(II) diethyldithiocarbamate, Cu(DDC) 2 , is the crucial DSF's metabolite exhibiting anticancer activity. In this paper, highly stable polymeric nanoparticles were fabricated via a coordination strategy between Cu(II) and carboxylic groups in poly(ethylene glycol)-b-poly(ester-carbonate) (PEC) for efficient loading of Cu(DDC) 2 , which was generated by the in situ reaction of DSF and Cu(II). The properties of nanoparticles such as drug loading contents, sizes, and morphologies could be tuned by varying the feeding ratios of DSF, Cu(II), and PEC. These Cu(II)/DDC-loaded nanoparticles showed excellent stability in both neutral and weak acidic solutions and under dilution. In vitro anticancer study established that Cu(II)/DDC-loaded nanoparticles could enable a combination therapy of Cu(DDC) 2 -based chemotherapy and chemodynamic therapy mediated by bioavailable Cu(II) that was not in the form of Cu(DDC) 2 . The in vivo antitumor results demonstrated that the Cu(II)/DDC-loaded nanoparticles showed superior antitumor efficacy to DSF/Cu(II). Our study provided a facile and effective strategy of highly stable coordination-mediated polymeric nanoparticles for combinational therapy of cancer.

RETRACTED: Disulfiram Chelated With Copper Inhibits the Growth of Gastric Cancer Cells by Modulating Stress Response and Wnt/β-catenin Signaling

“…Furthermore, the anti-cancer activity of DSF has been explored since 1977 ( 17 ). DSF is rapidly converted to diethyldithiocarbamate in the system, which forms a stable complex with Cu; the complex exhibits a stronger anti-tumor effect than DSF alone ( 18 ). DSF/Cu complex has been reported to suppress the growth and metastasis of non-small-cell lung cancer (NSCLC), hepatocellular carcinoma, and oral squamous cell carcinoma ( 6 , 19 , 20 ).…”

“…As this study was originally designed to explore the role of DSF/Cu in inhibiting the growth of GC cells, a positive control was not used; this is a limitation of the current study. Multiple studies have demonstrated that DSF-nanoparticles have enhanced anti-cancer effect ( 18 ). In the future, we plan to perform nano-modification of DSF and use docetaxel as a positive control to further explore the role of DSF in cancer.…”

The Coppery Age: Copper (Cu)‐Involved Nanotheranostics

“…The design of coordinated polymer nanoparticles with the encapsulation of Cu(II) diethyldithiocarbamate (Cu(DDC) 2 ) exhibited synergistic therapeutic outcome of chemotherapy and CDT, where Cu(DDC) 2 exerted the chemotherapeutic function and the additional bioavailable Cu(II) out of Cu(DDC) 2 catalyzed the production of hydroxyl radicals in oxidative tumor therapy. [202] The construction of Cu 2−x E-Au (E = S, Se) heteronanostructure concurrently achieved augmented attenuation Figure 22. Schematic illustration of the underlying synergistic therapeutic mechanism of copper(I) phosphide nanocrystals (CP NCs) for multimodality imaging-guided photothermal ablation and photothermal-enhanced CDT of the deep-seated tumor.…”

“…The design of coordinated polymer nanoparticles with the encapsulation of Cu(II) diethyldithiocarbamate (Cu(DDC) 2 ) exhibited synergistic therapeutic outcome of chemotherapy and CDT, where Cu(DDC) 2 exerted the chemotherapeutic function and the additional bioavailable Cu(II) out of Cu(DDC) 2 catalyzed the production of hydroxyl radicals in oxidative tumor therapy. [ 202 ]…”

Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix

“…These characteristics explain their higher accumulation in human oral epithelial carcinoma vincristine-resistant tumors (KBV) that further improved the efficacy of tumor theranostics, such as those using chemotherapy and photothermal therapy [76]. The [Cu(ddc) 2 ] (13) moiety coordinated to carboxylic groups from poly(ethylene glycol)-b-poly(ester-carbonate) generated a highly stable system able to inhibit A549 cells proliferation both in vitro and in vivo [77]. The interest for this bacc is generated by the fact that dsf exhibits an excellent in vitro antiproliferative activity mediated by (13) as its metabolite.…”