The complement system’s distinguishing feature is its cell-specific surface ligands. However, the limited scalability and complexity of incorporating surface-customizable ligands into membrane-bound cell-like microassemblages have hindered their widespread adoption in synthetic biology and bioengineering. Here, we present a method for the batch construction of polysaccharide-based microcapsules (polysaccharidosomes, P-somes) with intrinsic functional host membranes capable of docking guest ligands via facile host-guest interactions. beta-Cyclodextrin (beta-CD) conjugated to the microcapsule membrane building block serves as the host entity for guest adamantane-linked functional molecules Cyanine5 (Cy5) and Pam(3)CSK(4) (PAM). Interactive docking of either an aggregation agent, Cy5, or a Toll-like receptor agonist, Pam(3)CSK(4), on P-somes followed by incubation with macrophages resulted in aggregation and immune activation of macrophages, respectively. The specificity of host-guest interactions allows for the expedited incorporation of additional functionalities into microassemblages. This can be instrumental in engineering cell-like membrane surfaces that replicate genuine cell-cell interactions, offering a unified platform for the development of micrometer-sized programmable therapeutic protocells.
Xiong S, Mukwaya V, Yu X, Zeng Y, Wang L, Zhao W, and Dou H. (2025) Orthogonal Host-Guest Interactions Enable Programming of Protocell Membranes for Cellular High-Order Assembly and Enhanced Immunogenicity. ACS Appl Mater Interfaces 17(12):17979-17989 . [article]