bm9b00367_si_001.pdf (1.48 MB)
Highly Stable, Coordinated Polymeric Nanoparticles Loading Copper(II) Diethyldithiocarbamate for Combinational Chemo/Chemodynamic Therapy of Cancer
journal contribution
posted on 2019-05-22, 00:00 authored by Xinyu Peng, Qingqing Pan, Boya Zhang, Shiyu Wan, Sai Li, Kui Luo, Yuji Pu, Bin HeDisulfiram (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.