Nanotechnology connecting copper metabolism and tumor therapy

Abstract

Copper (Cu) is an essential trace element in the human body that is involved in the formation of several natural enzymes, such as superoxide dismutase and cyclooxygenase. Due to the high density of the outer electron cloud of Cu, which allows the transfer of multiple electrons, Cu is often used as the catalytic center in various metabolic enzymes. However, both deficiency and excessive accumulation of Cu can result in irreversible damage to cells. Therefore, strategies to regulate Cu metabolism, such as Cu exhaustion and Cu supplementation, have emerged as attractive approaches in anticancer therapy, due to the potential damages caused by Cu metabolism disorders. Notably, recent advancements in nanotechnology have enabled the development of nanomaterials that can regulate Cu metabolism, making this therapy applicable in vivo. In this review, we provide a systematic discussion of the physical and chemical properties of Cu and summarize the applications of nanotechnology in Cu metabolism‐based antitumor therapy. Finally, we outline the future directions and challenges of nano‐Cu therapy, emphasizing the scientific problems and technical bottlenecks that need to be addressed for successful clinical translation.

Advances and applications of nanoparticles in cancer therapy

“…Apart from killing cancer cells directly by their multifunction, such as angiogenesis, cuproptosis, apoptosis, pyroptosis, ferroptosis, and so forth, copper NPs have also been widely involved in catalytic therapy due to the high density of the outer electron cloud of copper, which in turn help solving some bottlenecks of chemotherapy, phototherapy, acoustic therapy. [183][184][185][186] In several biomedical applications, inorganic NPs, such as Au NPs and copper NPs, are also been utilized in the fields of catalysts, biosensors, bioimaging, and so forth. 183,187,188 These applications of inorganic NPs have been proved to significantly improve the effect of cancer therapy.…”

“…[183][184][185][186] In several biomedical applications, inorganic NPs, such as Au NPs and copper NPs, are also been utilized in the fields of catalysts, biosensors, bioimaging, and so forth. 183,187,188 These applications of inorganic NPs have been proved to significantly improve the effect of cancer therapy. [189][190][191] Furthermore, photocatalytic degradation of organic pollutants to small molecules without toxicity has been extensively explored for semi-conductor NPs and related nanomaterials, such as TiO 2 NPs, copper oxide NPs, and ZnO NPs.…”

“…Based on the special biological effects of these ions, such as copper ions, the generated ions or ion clusters after NP degradation may interfere with or hinder the metabolism and proliferation of tumor cells. 183 Moreover, as a drug delivery system, it is inevitable for NPs to cap the interference of TME, the limited tumor penetration depth, the drug-resistance of heterogeneous tumor cells, and the barrier of tumor mechanics. 1095,1096 Additionally, future NPs shall increasingly incorporate new molecular entities and novel classes of therapeutic agents as payloads, and make more efforts to surmount biological barriers and patient heterogeneity.…”