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.