Precise Deposition of Polydopamine on Cancer Cell Membrane as Artificial Receptor for Targeted Drug Delivery

Compared with conventional chemotherapy and radiotherapy, targeted molecular therapy, e.g., antibody-drug conjugates or aptamer-drug conjugates, can specifically identify overexpressed natural receptors on the cancer cell, perform targeted release of anticancer drugs, and achieve targeted killing of tumor cells. However, many natural receptors are also expressed on non-cancer cells, thereby diverting the targeting molecules to healthy cells. By generating artificial cell surface receptors specific to diseased cells, aptamer-drug conjugates can identify these artificial receptors, improve therapeutic efficacy, and decrease the minimum effective dosage. In this study, we use high K⁺ and high H₂O₂ of the tumor microenvironment (TME) to produce polydopamine only on living cancer cell membrane. Owing to the significant reactivity of polydopamine with amino groups, e.g., the amino group of proteins, polydopamine can deposit on tumor cells and act as "artificial receptors" for targeted delivery of anticancer drugs with amino groups, in other words, amino-containing drugs and protein drugs.