Abstract
The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H(2)S) 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 H(2)S. These gasotransmitters can be synergistically combined with traditional anticancer treatments such as radiotherapy, immunotherapy, chemotherapy, and phototherapy. Notably, NO, and more recently H(2)S, have been shown to reverse multidrug resistance. Nanomaterials to deliver NO donors and, to a lesser extent, H(2)S 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 H(2)S-releasing nanomaterials for anticancer effects. It also explores the interactions between NO and H(2)S, which are crucial for developing combined therapies and nanomedicines with minimal side effects.