In situ toxification of less toxic substance for the generation of effective anticarcinogens at the specific tumor tissue has been a novel paradigm for combating cancer. Significant efforts have been recently dedicated to turning clinical-approved drugs into anticancer agents in specific tumor microenvironment by chemical reactions. Herein, a hollow mesoporous Prussian blue (HMPB)-based therapeutic nanoplatform, denoted as DSF@PVP/Cu-HMPB, is constructed by encapsulating alcohol-abuse drug disulfiram (DSF) into the copper-enriched and polyvinylpyrrolidone (PVP)-decorated HMPB nanoparticles to achieve in situ chemical reaction-activated and hyperthermia-amplified chemotherapy of DSF. Upon tumor accumulation of DSF@PVP/Cu-HMPB, the endogenous mild acidity in tumor condition triggers the biodegradation of the HMPB nanoparticle and the concurrent co-releases of DSF and Cu2+ , thus forming cytotoxic bis(N,N-diethyl dithiocarbamato)copper(II) complexes (CuL2 ) via DSF-Cu2+ chelating reaction. Moreover, by the intrinsic photothermal-conversion effect of PVP/Cu-HMPBs, the anticancer effect of DSF is augmented by the hyperthermia generated upon near-infrared irradiation, thus inducing remarkable cell apoptosis in vitro and tumor elimination in vivo on both subcutaneous and orthotopic tumor-bearing models. This strategy of in situ drug transition by chemical chelation reaction and photothermal-augmentation provides a promising paradigm for designing novel cancer-therapeutic nanoplatforms.
Keywords: Prussian blue; disulfiram; hyperthermia-amplified chemotherapy; in situ toxification; tumor chemotherapy.
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