Carrier-Free Disulfiram Based Nanomedicine for Enhanced Cancer Therapy

Abstract

Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs. However, the carrier materials and intricate nature of multifunctional design always hindered the clinical transformation of nanomedicines. Herein, a novel carrier-free anticancer nanomedicine (CFDC) with tailored morphologies including nanodots, nanorod and nanosheet were prepared using the clinically approved anti-alcoholism drug disulfiram (DSF) via supramolecular assembly process. Our study reveals that CFDC induces the production of reactive oxygen species and activates the downstream apoptosis-related c-Jun N-terminal kinase (JNK) and p-38 pathway. In addition, the CFDC effectively counteract the inhibitory effect of NF-κB expression on ROS-induced cellular cytotoxicity, ultimately resulting in enhanced cell apoptosis, which is not achievable by pure DSF and the simply mixing of DSF and Cu²⁺ (DSF+Cu). Notably, the CFDC exhibits 3.1-, 3.0-folds increased on cancer cell DNA damage compared with the DSF, and DSF+Cu groups. In vivo experiments conducted on breast- or prostate-bearing mice modals demonstrated that the CFDC exhibits a higher efficacy in suppressing the tumor growth. The remarkable drug delivery efficiency and better anticancer effect of CFDC nanodrug provide promising prospects for the clinical transformation of DSF based nanodrug in cancer therapy.