Bioinspired cytomembrane coating besieges tumor for blocking metabolite transportation.

ABSTRACT

The metabolite transport inhibition of tumor cells holds promise to achieve anti-tumor efficacy. Herein, we presented an innovative strategy to hinder the delivery of metabolites through the in-situ besieging tumor cells with polyphenolic polymers that strongly adhere to the cytomembrane of tumor cells. Simultaneously, these polymers underwent self-crosslinking under the induction of tumor oxidative stress microenvironment to form an adhesive coating on the surface of the tumor cells. This polyphenol coating effectively obstructed glucose uptake, reducing metabolic products such as lactic acid, glutathione, and adenosine triphosphate, while also causing reactive oxygen species to accumulate in the tumor cells. The investigation of various tumor models, including 2D cells, 3D multicellular tumor spheroids, and xenograft tumors, demonstrated that the polyphenolic polymers effectively inhibited the growth of tumor cells by blocking key metabolite transport processes. Moreover, this highly adhesive coating could bind tumor cells to suppress their metastasis and invasion. This work identified polyphenolic polymers as a promising anticancer candidate with a mechanism by impeding the mass transport of tumor cells.