Copper-based nanoplatforms and their role in cancer therapy

Copper plays both an essential and potentially hazardous role for living systems. This assertion coupled with emerging evidences highlighting the pivotal role of copper in cancer progression, set the basis for advancing copper-based therapies in oncology. In the presence of copper nanostructures, the rules and mechanisms applying within cells to respond and regulate copper levels differ significantly from those governing copper in its ionic state. These different behaviors can be exploited by Nanotechnology to develop new therapeutic strategies against cancer. In this review, we focus on three of these scenarios: (i) disrupt the copper equilibrium either by artificially overloading copper in cancer cells, or depleting the indispensable endogenous copper required by cancer cells; (ii) leverage the synergy between copper nanostructures and other therapies, such as chemo-, radio- and photothermal therapy; (iii) describe the tools currently existing or under development to map and track copper nanostructures which are utilized in therapy, since they have the potential to unveil new cancer cell vulnerabilities. Finally, we elucidate the future pathways and obstacles facing nano-copper therapy in each particular section, highlighting the scientific complexities and practical challenges essential for its successful transition into clinical practice.