NO- and H2S- releasing nanomaterials: A crosstalk signaling pathway in cancer

The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H₂S) play important roles not only in maintaining physiological functions, but also in pathological conditions and events. Importantly, these molecules show a complex interplay in cancer biology, demonstrating both tumor-promoting and anti-tumor activities depending on their concentration, flux, and the environmental redox state. Additionally, various cell types respond differently to NO and H₂S. These gasotransmitters can be synergistically combined with traditional anticancer treatments such as radiotherapy, immunotherapy, chemotherapy, and phototherapy. Notably, NO, and more recently H₂S, have been shown to reverse multidrug resistance. Nanomaterials to deliver NO donors and, to a lesser extent, H₂S donors, have emerged as a promising approach for targeted delivery of these gasotransmitters. Nanotechnology has advanced the delivery of anticancer drugs, enhancing efficiency and reducing side effects on non-cancerous cells. This review highlights recent progress in the design of NO and H₂S-releasing nanomaterials for anticancer effects. It also explores the interactions between NO and H₂S, which are crucial for developing combined therapies and nanomedicines with minimal side effects.