Polyphenol -based controllable assembly platforms for reducing the risk of nonspecific adhesion in vivo for cancer therapy

Polyphenols, rich in phenolic structures, are widely found in plants and known for disturbing the cellular oxidative stress and regulating the signal pathways of tumor proliferation and metastasis, making them valuable in cancer therapy. Polyphenols display high adherence due to the presence of phenolic hydroxyl groups, which enables the formation of covalent and non-covalent interactions with different materials. However, nonspecific adhesion of polyphenols carries significant risks in in vivo applications as polyphenols might adhere to proteins and polysaccharides in the bloodstream or gastrointestinal tract, leading to thrombosis and lithiasis. Pre-occupying phenolic hydroxyl groups to construct controllable assembly platforms prior to in vivo application constitutes an effective strategy to enhance biosafety. In this review, we present the potential of polyphenols in cancer therapy and focus on strategies to reduce the risk of nonspecific adhesion. Nanoplatforms, films, and hydrogels are highlighted as the state-of-the-art safe assemblies of polyphenols, providing guidance for the design of safe and sophisticated polyphenol-based platforms, promoting a step forward in the clinical translation of polyphenol-based delivery strategies in cancer therapy.