Targeting Cancer Cells With Self‐Assembled Ru‐Polysaccharide Photocatalyst for Visible‐Light‐Induced Activation of Prodrugs

ABSTRACT Chemotherapy stands out as an effective cancer treatment, although typically accompanied by side effects arising from systemic toxicity of anticancer drugs due to the limited specific targeting of tumor cells. In this study, we present a self‐assembled Ru‐based polysaccharide photocatalyst that selectively targets cancer cells and catalyzes the prodrug‐to‐drug conversion upon exposure to visible light. The self‐assembled photocatalyst forms via supramolecular interactions between β‐cyclodextrins attached to the hyaluronic acid polymer and the adamantane‐functionalized tris(bipyridine)ruthenium(II) complex. This polymer supported photocatalysts enables precise targeting of cancer cells as it recognized the CD44 receptor, while the light driven conversion allows for temporal and spatial control over drug production. We demonstrate that both the pro‐probe (Rho‐N 3 ) and the prodrug (DOX‐L‐N 3 ) can be efficiently converted into the respective active compounds through visible light irradiation, using the supramolecular photocatalyst. The supramolecular photocatalyst targets MCF‐7 cancer cells over noncancerous NIH3T3 cells, converting Rho‐N 3 upon irradiation only when the catalyst is present in the cell. In line with this, irradiation of MCF‐7 cells that were exposed to DOX‐L‐N 3 induces increased cell death. This strategy is a way forward to efficient, controllable, and targeted activation of prodrugs within cancer cells.