Teaching new tricks to old dogs: A review of drug repositioning of disulfiram for cancer nanomedicine

Abstract

The increasing incidence and mortality of malignant tumors have required the development of diversified innovative therapies. Compared with the new therapeutic molecule invention, it is a more economical and efficient way to reposition old drugs that have been marketed or in clinical trials for tumor treatment. Studies have been carried out for repositioning the old approval drugs that are widely applied clinically with reliable biosafety and effectiveness evidence, including aspirin, artemisinin (and its derivatives, eg, dihydroartemisinin), metformin, and disulfiram (DSF). In addition to the approved pharmacological activity, these old drugs exhibited broad tumor‐suppressive effects. This review summarizes the drug repositioning strategy of DSF through nanotechnology and outlines the DSF nano‐formulations for cancer targeting delivery and therapy.

Current Advances on Nanomaterials Interfering with Lactate Metabolism for Tumor Therapy

“…Nanotechnology can integrate multiple therapeutic agents with different water solubility and pharmacokinetic characteristics into one platform, ensuring that agents with diverse therapeutic functions share the same pharmacokinetic fate during in vivo circulation. [ 29 ] Therefore, nanomaterials can maximize the efficacy of lactate metabolic regulation‐based multidrug combination therapies. Nanomaterials can directly or indirectly interfere with lactate metabolism due to their inherent biochemical activities. For example, some nanoparticles (e.g., SeNPs) can directly block lactate production in tumor cells by inhibiting the activity of glycolytic‐related enzymes.…”

“…[28] It is well known that one advantage of nanotherapeutics is their ability to integrate multiple therapeutic components into a single platform. [29] Therefore, researchers often load GLUT1 inhibitors on nanocarriers along with other therapeutic drugs to improve the overall therapeutic effect. For example, Jiang et al coloaded GLUT1 inhibitor (BAY-876) and Glucose transporters (i.e., GLUT1 and GLUT4) are responsible for the influx of glucose, which is then catalyzed by a series of glycolysis-related enzymes to produce lactate.…”

“…[ 28 ] It is well known that one advantage of nanotherapeutics is their ability to integrate multiple therapeutic components into a single platform. [ 29 ] Therefore, researchers often load GLUT1 inhibitors on nanocarriers along with other therapeutic drugs to improve the overall therapeutic effect. For example, Jiang et al coloaded GLUT1 inhibitor (BAY‐876) and doxorubicin prodrug (DOX‐Duplex) into a glutathione (GSH)‐responsive self‐assembled polymer nanocarrier (denoted as P‐B‐D) to achieve controlled release of different functional agents in tumor site ( Figure A).…”

Cancer nanotechnology: current status and perspectives

“…A new development of a TRAIL-active trimer ferritin nanocage (TRAIL-ATNC) has 16 times longer serum half-life while maintaining anti-tumor efficacy in vivo in xenograft breast cancer and orthotopic pancreatic models [ 64 ]. Nanoformulation has the potential to improve PK/PD parameters for any therapeutic, opening the door to drug repurposing [ 214 ]. Recently, lipid tail modifications of cationic liposomes were shown to increase the loading capacity of highly hydrophobic PTX helpful for the development of liposomal delivery of PTX to reduce the side effects and cost.…”

“…A new development of a TRAIL-active trimer ferritin nanocage (TRAIL-ATNC) has 16 times longer serum half-life while maintaining anti-tumor efficacy in vivo in xenograft breast cancer and orthotopic pancreatic models [64]. Nanoformulation has the potential to improve PK/PD parameters for any therapeutic, opening the door to drug repurposing [214].…”