Metal‐Coordinated Adsorption of Nanoparticles to Macrophages for Targeted Cancer Therapy

Abstract Living cell‐based drug delivery systems (LC‐DDSs) are limited by adverse interactions between drugs and carrier cells, typically drug‐induced toxicity to carrier cells and restriction of carrier cells on drug release. Here, a method is established to adsorb nanocarriers externally to living cells, thereby reducing cytotoxicity caused by drug uptake and realizing improved drug release at the disease site. It is found that a divalent metal ion‐phenolic network (MPN) affords adhesion of poly (lactic‐co‐glycolic acid) nanoparticles onto macrophage (Mφ) surfaces with minimized intracellular uptake and no negative effect on cell proliferation. On this basis, an Mφ‐DDS with doxorubicin‐loaded nanoparticles on cell surface (DOX‐NP@Mφ) is constructed. Compared to intracellular loading via endocytosis, this method well‐maintains bioactivity (viability and migration chemotaxis) of the carrier cell. By virtue of the photothermal effect of MPN at the tumor site, DOX‐NP‐associated vesicles are liberated for improved chemotherapy. This facile, benign, and efficient method (ice bath, 2 min) for extracellular nanoparticle attachment and minimizing intracellular uptake provides a platform technology for LC‐DDS development.