Programmable Membrane-Mediated Attachment of Synthetic Virus-like Nanoparticles on Artificial Protocells for Enhanced Immunogenicity

Summary The programming of protocells to implement and control the functions of living cells through activated membrane receptor signaling remains a challenge for the development of protoliving technologies. Here, we report a synthetic protocell capable of inducing high levels of macrophage activation in vitro. An immunogenic protocell comprising hyaluronic acid (HA)-polymer membrane decorated with synthetic virus-like particles derived from the functionalization of core-shell polymer nanoparticles with a Toll-like receptor agonist (Pam3SK4) and cell/protocell membrane-binding lectin (WGA) is fabricated. While the non-decorated HA-based protocells and functionalized SVLPs alone initiate moderate levels of macrophage activation, co-presentation of WGA and Pam3SK4 on the protocell membrane results in hyperactivation of the phagocytes via a synergistic multi-receptor process. This work offers opportunities for developing chemically programmable soft microscale agents capable of eliciting cellular signal transduction and genetic outputs and provides a step toward implementing future therapeutic strategies based on cognate interactions at the cell-protocell interface.