Engineering metal-organic framework-based smart porous nanoplatforms for targeted therapy and theranostic applications.

Metal-organic frameworks (MOFs) are materials that have recently emerged with the potential for various biomedical applications. Through engineering MOFs to contain various components and functionalities, they have progressed from porous materials to "smart" MOFs that can deliver payloads to cells, release the payloads in specific situations, perform certain therapies on the cells, and even perform diagnosis and therapy procedures simultaneously. This review aims to highlight the synergistic induction of ferroptosis through nanomedicine, immunotherapy, and targeted therapeutic agents for the treatment of breast and gastrointestinal (GI) malignancies. Nanotechnology-based targeted delivery systems enhance the delivery of ferroptosis-inducing agents to cancer cells while minimizing the toxicity of these agents to healthy cells. Additionally, immunotherapeutic agents enhance the immune response to cancer cells and sensitize them to ferroptotic cell death. Targeted therapeutic agents that act on the molecular regulators of ferroptosis, such as GPX4, System Xc-, NRF2, and iron metabolism, potentiate ferroptosis. The combination of these therapeutic strategies has the potential to reverse multidrug resistance, limit metastasis, and increase the efficacy of cancer therapy. Furthermore, this review discusses the current advances in and future perspectives on the development of combination therapies targeting ferroptotic cell death in cancer cells. The integration of nanomedicine, immunotherapy, and targeted therapeutic agents presents a highly promising new avenue for treating breast and gastrointestinal cancers.