Engineering metal‐phenolic networks for enhancing cancer therapy by tumor microenvironment modulation

The complicated tumor microenvironment (TME) is featured by low pH values, high redox status, and hypoxia, which greatly supports the genesis, development, and metastasis of tumors, leading to drug resistance and clinical failure. Moreover, a lot of immunosuppressive cells infiltrate in such TME, resulting in depressing immunotherapy. Therefore, the development of TME-responsive nanoplatforms has shown great significance in enhancing cancer therapeutics. Metal-phenolic networks (MPNs)-based nanosystems, which self-assemble via coordination of phenolic materials and metal ions, have emerged as excellent TME theranostic nanoplatforms. MPNs have unique properties including fast preparation, tunable morphologies, pH response, and biocompatibility. Besides, functionalization and surface modification can endow MPNs with specific functions for application requirements. Here, the representative engineering strategies of various polyphenols are first introduced, followed by the introduction of the engineering mechanisms of polyphenolic nanosystems, fabrication, and distinct properties of MPNs. Then, their advances in TME modulation are highlighted, such as antiangiogenesis, hypoxia relief, combination therapy sensitization, and immunosuppressive TME reversion. Finally, we will discuss the challenges and future perspectives of MPNs-based nanosystems for enhancing cancer therapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.