Harnessing engineered metal-phenolic networks as theranostic nanomedicines for cancer treatments

Nanomedicines leverage multifunctional components to engineer precise nanocarriers, with the goal of enhancing therapeutic outcomes while minimizing off-target effects in cancer treatments. However, the development of drug carriers integrating diagnostic and therapeutic functions faces significant challenges, including sophisticated synthetic routes, poor stability, limited biodegradability, and poor metabolization. Metal-phenolic networks (MPNs), a category of supramolecular amorphous networks fabricated by the coordinated self-assembly involving phenolic ligands and metal ions, have arisen as burgeoning candidates for biomedical application due to their facile fabrication, favorable biocompatibility, versatile loading capability, intrinsic biodegradability, and pH responsiveness, primarily functioning as multifunctional theranostic nanoformulations. In addition, surface engineering strategies enable the customization of MPNs to fulfill diverse application demands. Here, the strategies for constructing various types of MPNs are first summarized, succeeded by the presentation of distinct properties of MPNs. Then, their advancements in diverse programmed cell death (PCD) pathways, including apoptosis, ferroptosis, cuproptosis, pyroptosis, and disulfidptosis, together with bioimaging and corresponding induction of immunogenic cell death (ICD), are emphasized. Eventually, the principal constraints, current obstacles, and future perspectives regarding MPNs are offered and examined for enhancing cancer therapy. • The recent progress of preparation methods to fabricate metal-phenolic networks with different kinds of morphologies. • The summary of the distinctive capabilities and characteristics of metal-phenolic networks. • The recent advancements of metal-phenolic networks in diverse programmed cell death pathways, including apoptosis, ferroptosis, cuproptosis, pyroptosis, and disulfidptosis, together with bioimaging and corresponding induction of immunogenic cell death. • Discussion about challenges and prospects of metal-phenolic networks for theranostics nanoformulations.